PUBLICATIONS
Publication Portfolio
2024
Khan, T., Waseem, R., Shahid, M., Ansari, J., Hassan, M. I., Shamsi, A., & Islam, A. (2024). Understanding the Modulation of α-Synuclein Fibrillation by N-Acetyl Aspartate: A Brain Metabolite. ACS omega, 9(10), 12262–12271. https://doi.org/10.1021/acsomega.4c00595
Iram, F., Shahid, M., Ansari, J., Ashraf, G. M., Hassan, M. I., & Islam, A. (2024). Navigating the Maze of Alzheimer’s Disease by Exploring BACE1: Discovery, Current Scenario, and Future Prospects. Ageing research reviews, 102342. Advance online publication. https://doi.org/10.1016/j.arr.2024.102342
Khan, T., Waseem, R., Shahid, M., Ansari, J., Ahanger, I. A., Hassan, I., & Islam, A. (2023). Recent advancement in therapeutic strategies for Alzheimer’s disease: Insights from clinical trials. Ageing research reviews, 92, 102113. https://doi.org/10.1016/j.arr.2023.102113
Bashir, S., Aiman, A., Chaudhary, A. A., Khan, N., Ahanger, I. A., Sami, N., Almugri, E. A., Ali, M. A. M., Khan, S. U., Shahid, M., Basir, S. F., Hassan, M. I., & Islam, A. (2024). Probing protein aggregation through spectroscopic insights and multimodal approaches: A comprehensive review for counteracting neurodegenerative disorders. Heliyon, 10(7), e27949. https://doi.org/10.1016/j.heliyon.2024.e27949
Taiyab, A., Choudhury, A., Haidar, S., Yousuf, M., Rathi, A., Koul, P., Chakrabarty, A., Islam, A., Shamsi, A., & Hassan, M. I. (2024). Exploring MTH1 inhibitory potential of Thymoquinone and Baicalin for therapeutic targeting of breast cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 173, 116332. https://doi.org/10.1016/j.biopha.2024.116332
Choudhir, G., Shahid, M., & Islam, A. (2024). Elucidating the pH-Dependent Conformational Transitions of Eryngin: Insights from Molecular Dynamics Simulations. Informatics in Medicine Unlocked, 101508.
Taiyab, A., Haider, S., Choudhury, A., Rathi, A., Hussain, A., Alajmi, M. F., … & Hassan, M. I. (2024). Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy. https://doi.org/10.21203/rs.3.rs-4365362/v1
Taiyab, A., Haider, S., Choudhury, A., Rathi, A., Hussain, A., Alajmi, M. F., … & Hassan, M. I. (2024). Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy. https://doi.org/10.21203/rs.3.rs-4365362/v1
Bashir, S., Aiman, A., Shahid, M., Chaudhary, A. A., Sami, N., Basir, S. F., Hassan, I., & Islam, A., Professor (2024). Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology. Ageing research reviews, 96, 102276. https://doi.org/10.1016/j.arr.2024.102276
2025
Faiza Iram Ayesha Aiman, Danish Alam
Biophysical insights into pH-induced structural dynamics of recombinant interferon β-1b: Aggregation under acidic conditions Journal Article
In: International Journal of Biological Macromolecules, vol. 318, iss. 3, pp. 145128, 2025.
@article{nokey,
title = {Biophysical insights into pH-induced structural dynamics of recombinant interferon β-1b: Aggregation under acidic conditions},
author = {Ayesha Aiman, Faiza Iram, Danish Alam, Seemi Farhat Basir, Luqman Ahmad Khan, Mohammad Shahid, Asimul Islam},
url = {https://www.sciencedirect.com/science/article/pii/S0141813025056818},
doi = {https://doi.org/10.1016/j.ijbiomac.2025.145128},
year = {2025},
date = {2025-06-11},
journal = {International Journal of Biological Macromolecules},
volume = {318},
issue = {3},
pages = {145128},
abstract = {Recombinant interferon beta-1b (rIFN β-1b) is a therapeutic protein used to treat multiple sclerosis (MS). This study investigates the influence of solution conditions on the structural conformation of rIFN β-1b for better pharmaceutical formulations. The structural properties of rIFN β were studied at various pH values (2.0–12.0) using multiple biophysical techniques. Far UV CD and FTIR analysis confirmed the presence of α-helices in the native confirmation of rIFN β-1b as well as in alkaline conditions, exclusively. pH-dependent exposure of the tryptophan residues was probed by neutral (acrylamide) and ionic (iodide) quenching studies. At pH 5.0–12.0, rIFNβ-1b formed collisional complex with tryptophan at the excited state (dynamic quenching). Dye-binding studies validated the tertiary structural measurements by binding to the exposed hydrophobic patches and revealed protein aggregation between pH 2.0–4.0 …},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recombinant interferon beta-1b (rIFN β-1b) is a therapeutic protein used to treat multiple sclerosis (MS). This study investigates the influence of solution conditions on the structural conformation of rIFN β-1b for better pharmaceutical formulations. The structural properties of rIFN β were studied at various pH values (2.0–12.0) using multiple biophysical techniques. Far UV CD and FTIR analysis confirmed the presence of α-helices in the native confirmation of rIFN β-1b as well as in alkaline conditions, exclusively. pH-dependent exposure of the tryptophan residues was probed by neutral (acrylamide) and ionic (iodide) quenching studies. At pH 5.0–12.0, rIFNβ-1b formed collisional complex with tryptophan at the excited state (dynamic quenching). Dye-binding studies validated the tertiary structural measurements by binding to the exposed hydrophobic patches and revealed protein aggregation between pH 2.0–4.0 …
Sumaiya Khan Arunabh Choudhury, Mohammad Umar Saeed
In: Biochemical and Biophysical Research Communications, vol. 775, pp. 152166, 2025.
@article{nokey,
title = {Structure-guided discovery of tau-phosphorylating kinase DYRK1A inhibitors for therapeutic targeting of neuroinflammatory diseases: Insights from microsecond MD simulation and MMPBSA analyses},
author = {Arunabh Choudhury, Sumaiya Khan, Mohammad Umar Saeed, Taj Mohammad, Afzal Hussain, Mohamed F AlAjmi, Urooj Fatima, Asimul Islam, Md Imtaiyaz Hassan},
url = {https://www.sciencedirect.com/science/article/pii/S0006291X25008812},
doi = {https://doi.org/10.1016/j.bbrc.2025.152166},
year = {2025},
date = {2025-06-08},
urldate = {2025-06-08},
journal = {Biochemical and Biophysical Research Communications},
volume = {775},
pages = {152166},
abstract = {Tauopathies are a class of nearly 20 neurodegenerative diseases, classified into primary and secondary tauopathies. Alzheimer's disease (AD) is a type of secondary tauopathy in which abnormal phosphorylation of tau proteins takes place, which is linked to the kinase activity of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). Overexpression of DYRK1A hyperphosphorylates the tau protein, leading to its aggregation. Inhibiting DYRK1A activity can be a promising strategy to prevent tau hyperphosphorylation. In this study, we conducted a virtual screening of natural bioactive compounds from the ZINC database to identify potential small-molecule inhibitors of DYRK1A. The analyses revealed two compounds, ZINC08300244 and ZINC08964763, which showed a high binding affinity with DYRK1A and appropriate pharmacokinetic properties. Density functional theory (DFT) analysis of these two compounds was performed, and their stability of interaction with DYRK1A was further analysed by all-atom molecular dynamics (MD) simulations for 1 μs. Analysis of the MD trajectories was also performed using MM/PBSA and per-residue binding free energy decomposition. The results indicated the stable complex formation of DYRK1A with the two selected molecules for DYRK1A inhibition to prevent tau-hyperphosphorylation. This study highlights the use of virtual screening and MD simulations in finding natural product-based inhibitors of DYRK1A, which may lead to the development of novel therapeutic strategies for treating neuroinflammatory diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tauopathies are a class of nearly 20 neurodegenerative diseases, classified into primary and secondary tauopathies. Alzheimer's disease (AD) is a type of secondary tauopathy in which abnormal phosphorylation of tau proteins takes place, which is linked to the kinase activity of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). Overexpression of DYRK1A hyperphosphorylates the tau protein, leading to its aggregation. Inhibiting DYRK1A activity can be a promising strategy to prevent tau hyperphosphorylation. In this study, we conducted a virtual screening of natural bioactive compounds from the ZINC database to identify potential small-molecule inhibitors of DYRK1A. The analyses revealed two compounds, ZINC08300244 and ZINC08964763, which showed a high binding affinity with DYRK1A and appropriate pharmacokinetic properties. Density functional theory (DFT) analysis of these two compounds was performed, and their stability of interaction with DYRK1A was further analysed by all-atom molecular dynamics (MD) simulations for 1 μs. Analysis of the MD trajectories was also performed using MM/PBSA and per-residue binding free energy decomposition. The results indicated the stable complex formation of DYRK1A with the two selected molecules for DYRK1A inhibition to prevent tau-hyperphosphorylation. This study highlights the use of virtual screening and MD simulations in finding natural product-based inhibitors of DYRK1A, which may lead to the development of novel therapeutic strategies for treating neuroinflammatory diseases.
Shabina Mehtab Gourav Choudhir, Mohammad Shahid
In: Next Research, vol. 2, iss. 2, pp. 100327, 2025.
@article{nokey,
title = {Computational evaluation of Jeevamrutha metabolites binding affinity to MurE enzyme of Xanthomonas oryzae pv. oryzae for bacterial disease management},
author = {Gourav Choudhir, Shabina Mehtab, Mohammad Shahid, Faiza Iram, Anas Shamsi, Anwar Ahmed, Asimul Islam},
url = {https://www.sciencedirect.com/science/article/pii/S3050475925001988},
doi = {https://doi.org/10.1016/j.nexres.2025.100327},
year = {2025},
date = {2025-06-01},
journal = {Next Research},
volume = {2},
issue = {2},
pages = {100327},
abstract = {This study explores metabolites derived from Jeevamrutha, a traditional Indian agricultural practice commonly employed to manage crop health. Jeevamrutha offers a potential alternative to chemical pesticides, which harm the ecosystem and human well-being. This investigation utilized computational modeling to identify metabolites in Jeevamrutha that could bind to and inhibit MurE, an enzyme critical for bacterial cell wall synthesis, bacterial growth, and infections. Two hundred eighty-one Jeevamrutha metabolites were selected from the literature, and their binding energies with MurE were evaluated. The binding energies of the metabolites ranged from -3.3 to -8.7 kcal/mol. Metabolites with a binding energy of -8.0 kcal/mol or less were selected for interaction and toxicity analyses. Among the molecules considered, 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene demonstrated a binding affinity of -8.4 kcal/mol and an LD50 of 10,000 mg/kg. Furthermore, molecular dynamics simulation results suggest that 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene forms stable interactions with MurE. These results indicate that 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene can potentially control bacterial diseases in agricultural fields. Optimizing Jeevamrutha for beneficial metabolite production could enhance agricultural productivity. Further research is required to confirm these results, including in vitro and in vivo experiments. This research contributes to the development of sustainable and safe agricultural practices. It is also possible that a Jeevamrutha formulation could improve the soil quality of fallow fields, potentially restoring their productivity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This study explores metabolites derived from Jeevamrutha, a traditional Indian agricultural practice commonly employed to manage crop health. Jeevamrutha offers a potential alternative to chemical pesticides, which harm the ecosystem and human well-being. This investigation utilized computational modeling to identify metabolites in Jeevamrutha that could bind to and inhibit MurE, an enzyme critical for bacterial cell wall synthesis, bacterial growth, and infections. Two hundred eighty-one Jeevamrutha metabolites were selected from the literature, and their binding energies with MurE were evaluated. The binding energies of the metabolites ranged from -3.3 to -8.7 kcal/mol. Metabolites with a binding energy of -8.0 kcal/mol or less were selected for interaction and toxicity analyses. Among the molecules considered, 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene demonstrated a binding affinity of -8.4 kcal/mol and an LD50 of 10,000 mg/kg. Furthermore, molecular dynamics simulation results suggest that 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene forms stable interactions with MurE. These results indicate that 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene can potentially control bacterial diseases in agricultural fields. Optimizing Jeevamrutha for beneficial metabolite production could enhance agricultural productivity. Further research is required to confirm these results, including in vitro and in vivo experiments. This research contributes to the development of sustainable and safe agricultural practices. It is also possible that a Jeevamrutha formulation could improve the soil quality of fallow fields, potentially restoring their productivity.
Faiza Iram Gourav Choudhir, Mohammad Shahid
In: Aspects of Molecular Medicine, vol. 5, pp. 100076, 2025.
@article{nokey,
title = {Antibacterial potential of Trichoderma bioactive metabolites in managing Staphylococcus aureus infection: Integrated molecular modeling approaches},
author = {Gourav Choudhir, Faiza Iram, Mohammad Shahid, Anas Shamsi, Md Imtaiyaz Hassan, Asimul Islam},
url = {https://www.sciencedirect.com/science/article/pii/S2949688825000140},
doi = {https://doi.org/10.1016/j.amolm.2025.100076},
year = {2025},
date = {2025-06-01},
urldate = {2025-06-01},
journal = {Aspects of Molecular Medicine},
volume = {5},
pages = {100076},
abstract = {Staphylococcus aureus is a primary hospital-acquired infection-causing bacteria that is becoming resistant to many antibiotics. Its infection sites range from skin to soft tissue. The development of drugs for managing Staphylococcus aureus infection is urgently required. Targeting the enzymes involved in bacteria maintaining the integrity of cell walls could provide advances compared to other targets. Integrating molecular modeling approaches with drug-likeness properties identified the metabolites with affinity and safety to use. Molecular docking results showed that three metabolites with promising binding affinities to FmtA and interactions with the vital amino acid residues are essential in catalytic activity. The drug likeliness analysis showed that selected metabolites do not have any violations of Lipinski rules. A molecular dynamics simulation study revealed that metabolites, bisorbibutenolide and Koninginin A, exhibited the most stable complexes with FmtA. Bisorbibutenolide and Koninginin A also formed hydrogen bonds with FmtA throughout the simulation. These findings suggest that bisorbibutenolide and Koninginin A have the potential for further development as an anti-Staphylococcus aureus agent via targeting FmtA. Moreover, comprehensive experimental studies are necessary to validate these computational findings.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Staphylococcus aureus is a primary hospital-acquired infection-causing bacteria that is becoming resistant to many antibiotics. Its infection sites range from skin to soft tissue. The development of drugs for managing Staphylococcus aureus infection is urgently required. Targeting the enzymes involved in bacteria maintaining the integrity of cell walls could provide advances compared to other targets. Integrating molecular modeling approaches with drug-likeness properties identified the metabolites with affinity and safety to use. Molecular docking results showed that three metabolites with promising binding affinities to FmtA and interactions with the vital amino acid residues are essential in catalytic activity. The drug likeliness analysis showed that selected metabolites do not have any violations of Lipinski rules. A molecular dynamics simulation study revealed that metabolites, bisorbibutenolide and Koninginin A, exhibited the most stable complexes with FmtA. Bisorbibutenolide and Koninginin A also formed hydrogen bonds with FmtA throughout the simulation. These findings suggest that bisorbibutenolide and Koninginin A have the potential for further development as an anti-Staphylococcus aureus agent via targeting FmtA. Moreover, comprehensive experimental studies are necessary to validate these computational findings.
Asimul Islam Anam Bakhtiyar, Romana Ishrat
AI-driven approaches in therapeutic interventions: Transforming RNA-seq analysis into biomarker discovery and drug development Journal Article
In: Drug Discovery Today, vol. 30, iss. 7, pp. 104391, 2025.
@article{nokey,
title = { AI-driven approaches in therapeutic interventions: Transforming RNA-seq analysis into biomarker discovery and drug development},
author = {Anam Bakhtiyar, Asimul Islam, Romana Ishrat, Md Imtaiyaz Hassan},
url = {https://www.sciencedirect.com/science/article/pii/S1359644625001047},
doi = {https://doi.org/10.1016/j.drudis.2025.104391},
year = {2025},
date = {2025-05-29},
journal = {Drug Discovery Today},
volume = {30},
issue = {7},
pages = {104391},
abstract = {Pharmacotranscriptomics integrates transcriptomics and pharmacology to discover potential therapeutic targets for effective treatment. This review focuses on significant advancements in combining artificial intelligence (AI) with transcriptomic research, enabling the conversion of vast data sets into valuable knowledge for for developing effective therapeutics. We provide detailed insights into implementing machine learning (ML) techniques for analyzing intricate transcriptomic data, facilitating a comprehensive understanding of disease mechanisms and the identification of key signature genes for biomarker and drug development. We further highlighted the potential of ML to streamline the drug discovery process by revealing disease mechanisms and suggesting therapeutic interventions. This review presents a comprehensive framework of AI models and their applications within pharmacotranscriptomics analysis. We also discuss the challenges and limitations needed to optimize AI models for enhanced therapeutic outcomes.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pharmacotranscriptomics integrates transcriptomics and pharmacology to discover potential therapeutic targets for effective treatment. This review focuses on significant advancements in combining artificial intelligence (AI) with transcriptomic research, enabling the conversion of vast data sets into valuable knowledge for for developing effective therapeutics. We provide detailed insights into implementing machine learning (ML) techniques for analyzing intricate transcriptomic data, facilitating a comprehensive understanding of disease mechanisms and the identification of key signature genes for biomarker and drug development. We further highlighted the potential of ML to streamline the drug discovery process by revealing disease mechanisms and suggesting therapeutic interventions. This review presents a comprehensive framework of AI models and their applications within pharmacotranscriptomics analysis. We also discuss the challenges and limitations needed to optimize AI models for enhanced therapeutic outcomes.
Anas Shamsi Gourav Choudhir, Mohammad Shahid
Targeting Rice Blast Disease: Evaluating Binding Affinity of Trichoderma Metabolite to Pyricularia oryzae GSK-1 through Molecular Modeling Approaches Bachelor Thesis
2025.
@bachelorthesis{nokey,
title = {Targeting Rice Blast Disease: Evaluating Binding Affinity of Trichoderma Metabolite to Pyricularia oryzae GSK-1 through Molecular Modeling Approaches},
author = {Gourav Choudhir, Anas Shamsi, Mohammad Shahid, Anwar Ahmed, Md Imtaiyaz Hassan, Asimul Islam},
year = {2025},
date = {2025-04-28},
journal = {Next Research},
volume = {2},
issue = {2},
pages = {100363},
abstract = {Rice blast disease, caused by the fungus Pyricularia oryzae, is a significant threat to global rice production. Managing rice blasts by inhibiting key enzymes involved in the pathogenesis and development of Pyricularia oryzae is advantageous. In this study, we investigated the potential of Trichoderma species metabolites to manage rice blast disease by inhibiting GSK-1, a crucial enzyme in the fungus's development and pathogenesis. Molecular docking and molecular dynamics simulation results showed that Trichotetronine and Bisorbibutenolide have a higher tendency with GSK-1 regarding binding affinity and stability. Molecular docking revealed that both metabolites interact with crucial amino acid residues at the GSK-1 catalytic sites. Further, molecular dynamics simulations suggested stable interactions between GSK-1 and selected metabolites throughout the simulation. These findings highlight Trichotetronine and Bisorbibutenolide as possible candidates for managing rice blast disease. However, further studies are needed to validate their efficacy for managing Pyricularia oryzae infection using experimental methods.},
keywords = {},
pubstate = {published},
tppubtype = {bachelorthesis}
}
Rice blast disease, caused by the fungus Pyricularia oryzae, is a significant threat to global rice production. Managing rice blasts by inhibiting key enzymes involved in the pathogenesis and development of Pyricularia oryzae is advantageous. In this study, we investigated the potential of Trichoderma species metabolites to manage rice blast disease by inhibiting GSK-1, a crucial enzyme in the fungus's development and pathogenesis. Molecular docking and molecular dynamics simulation results showed that Trichotetronine and Bisorbibutenolide have a higher tendency with GSK-1 regarding binding affinity and stability. Molecular docking revealed that both metabolites interact with crucial amino acid residues at the GSK-1 catalytic sites. Further, molecular dynamics simulations suggested stable interactions between GSK-1 and selected metabolites throughout the simulation. These findings highlight Trichotetronine and Bisorbibutenolide as possible candidates for managing rice blast disease. However, further studies are needed to validate their efficacy for managing Pyricularia oryzae infection using experimental methods.
Abdus Samad Tanzeel Khan, Rashid Waseem
In: ACS Chemical Neuroscience, vol. 16, iss. 9, pp. 1767–1779, 2025.
@article{nokey,
title = {Delineating the Mechanistic Insight of Inhibition of α-Synuclein Fibrillation by Neuro Metabolite, Myo-inositol: Implications in Synucleopathies-Related Disorders},
author = {Tanzeel Khan, Abdus Samad, Rashid Waseem, Ayesha Tazeen, Mohammad Shahid, Shama Parveen, Md Imtaiyaz Hassan, Asimul Islam},
url = {https://pubs.acs.org/doi/full/10.1021/acschemneuro.4c00843},
doi = {https://doi.org/10.1021/acschemneuro.4c00843},
year = {2025},
date = {2025-04-22},
urldate = {2025-04-22},
journal = {ACS Chemical Neuroscience},
volume = {16},
issue = {9},
pages = {1767–1779},
abstract = {The fibrillation of α-synuclein (α-syn) is a major factor contributing to neuronal damage and is critical in developing synucleopathies-related disorders. Considering this, the discovery of new compounds that can inhibit or modulate α-syn aggregation is a significant area of research. While polyol osmolytes have been shown to reduce α-syn fibrillation, the impact of brain metabolites such as myo-inositol (MI) on α-syn aggregation has not yet been explored. This study is the first to examine the effects of MI on α-syn aggregation, utilizing spectroscopic, microscopic, and cell cytotoxicity assay. Various aggregation assays revealed that MI inhibits the α-syn fibrillation in a dose-dependent manner. Fluorescence microscopy observations suggest that MI inhibits the α-syn fibrillation by forming amorphous aggregates. MTT assay revealed that α-syn aggregates in the presence of different concentrations of MI were not toxic as compared to α-syn fibrils. Thus, the mechanistic insight of inhibition of α-syn fibrillation by MI was explored by employing interaction studies using spectroscopic, calorimetric, and in silico approaches. Surface plasmon resonance and isothermal titration calorimetry suggest that MI-α-syn interacted with significant binding affinity, and the reaction was spontaneous. Molecular docking results depict that MI interacted with the aggregation-prone residues (36–42) at the N-terminal of α-syn, thereby stabilizing the α-syn and preventing the fibril formation. Molecular dynamics simulation results demonstrate the stability of the complex formation of MI with α-syn. This study highlighted the mechanistic insight of MI on preventing the α-syn from forming amyloid fibril, which could be further explored for therapeutic management of synucleopathies-related disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The fibrillation of α-synuclein (α-syn) is a major factor contributing to neuronal damage and is critical in developing synucleopathies-related disorders. Considering this, the discovery of new compounds that can inhibit or modulate α-syn aggregation is a significant area of research. While polyol osmolytes have been shown to reduce α-syn fibrillation, the impact of brain metabolites such as myo-inositol (MI) on α-syn aggregation has not yet been explored. This study is the first to examine the effects of MI on α-syn aggregation, utilizing spectroscopic, microscopic, and cell cytotoxicity assay. Various aggregation assays revealed that MI inhibits the α-syn fibrillation in a dose-dependent manner. Fluorescence microscopy observations suggest that MI inhibits the α-syn fibrillation by forming amorphous aggregates. MTT assay revealed that α-syn aggregates in the presence of different concentrations of MI were not toxic as compared to α-syn fibrils. Thus, the mechanistic insight of inhibition of α-syn fibrillation by MI was explored by employing interaction studies using spectroscopic, calorimetric, and in silico approaches. Surface plasmon resonance and isothermal titration calorimetry suggest that MI-α-syn interacted with significant binding affinity, and the reaction was spontaneous. Molecular docking results depict that MI interacted with the aggregation-prone residues (36–42) at the N-terminal of α-syn, thereby stabilizing the α-syn and preventing the fibril formation. Molecular dynamics simulation results demonstrate the stability of the complex formation of MI with α-syn. This study highlighted the mechanistic insight of MI on preventing the α-syn from forming amyloid fibril, which could be further explored for therapeutic management of synucleopathies-related disorders.
Faiza Iram Gourav Choudhir, Mohammad Shahid
Inhibition potential of margolonone and isomargolonone against the dengue virus protease using molecular modeling approaches Journal Article
In: Frontiers in Bioinformatics, vol. 5, pp. 1517115, 2025.
@article{nokey,
title = {Inhibition potential of margolonone and isomargolonone against the dengue virus protease using molecular modeling approaches},
author = {Gourav Choudhir, Faiza Iram, Mohammad Shahid, Anas Shamsi, Md Imtaiyaz Hassan, Asimul Islam},
url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11979248/},
doi = {https://doi.org/10.3389/fbinf.2025.1517115},
year = {2025},
date = {2025-03-26},
urldate = {2025-03-26},
journal = {Frontiers in Bioinformatics},
volume = {5},
pages = {1517115},
abstract = {Background
Dengue is a mosquito-borne viral disease with no cure. Inhibiting key enzymes vital in replication could manage the dengue virus infection. This study investigated the potential of margolonone and isomargolonone from Azadirachta indica to inhibit dengue virus replication.
Methods
The 3D structure of margolonone and isomargolonone were obtained from the PubChem database. The drug-likeness properties of these molecules were performed using a Swiss-ADME server. The molecular docking and molecular dynamics simulation assessed binding affinity and interactions.
Results
The drug-likeness of parameters showed that Margolonone and isoMargolonone showed zero violation of Lipinski rules. Docking simulations showed that both compounds bind to the active site of a critical enzyme (NS3 protease) essential for viral replication. Molecular dynamics simulations suggested that isomargolonone may bind more stably to NS3 than margolonone. Additionally, MMPBSA analysis showed that Margolonone does not show favorable binding energy.
Conclusion
These findings warrant further investigation of isomargolonone as a potential anti-dengue drug. Further in-vitro and in-vivo evaluations need to be done before accepting it as drug molecules.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Dengue is a mosquito-borne viral disease with no cure. Inhibiting key enzymes vital in replication could manage the dengue virus infection. This study investigated the potential of margolonone and isomargolonone from Azadirachta indica to inhibit dengue virus replication.
Methods
The 3D structure of margolonone and isomargolonone were obtained from the PubChem database. The drug-likeness properties of these molecules were performed using a Swiss-ADME server. The molecular docking and molecular dynamics simulation assessed binding affinity and interactions.
Results
The drug-likeness of parameters showed that Margolonone and isoMargolonone showed zero violation of Lipinski rules. Docking simulations showed that both compounds bind to the active site of a critical enzyme (NS3 protease) essential for viral replication. Molecular dynamics simulations suggested that isomargolonone may bind more stably to NS3 than margolonone. Additionally, MMPBSA analysis showed that Margolonone does not show favorable binding energy.
Conclusion
These findings warrant further investigation of isomargolonone as a potential anti-dengue drug. Further in-vitro and in-vivo evaluations need to be done before accepting it as drug molecules.
Dengue is a mosquito-borne viral disease with no cure. Inhibiting key enzymes vital in replication could manage the dengue virus infection. This study investigated the potential of margolonone and isomargolonone from Azadirachta indica to inhibit dengue virus replication.
Methods
The 3D structure of margolonone and isomargolonone were obtained from the PubChem database. The drug-likeness properties of these molecules were performed using a Swiss-ADME server. The molecular docking and molecular dynamics simulation assessed binding affinity and interactions.
Results
The drug-likeness of parameters showed that Margolonone and isoMargolonone showed zero violation of Lipinski rules. Docking simulations showed that both compounds bind to the active site of a critical enzyme (NS3 protease) essential for viral replication. Molecular dynamics simulations suggested that isomargolonone may bind more stably to NS3 than margolonone. Additionally, MMPBSA analysis showed that Margolonone does not show favorable binding energy.
Conclusion
These findings warrant further investigation of isomargolonone as a potential anti-dengue drug. Further in-vitro and in-vivo evaluations need to be done before accepting it as drug molecules.
In: Viruses, vol. 17, iss. 3, pp. 402, 2025.
@article{nokey,
title = {Biochemical Screening of Phytochemicals and Identification of Scopoletin as a Potential Inhibitor of SARS-CoV-2 Mpro, Revealing Its Biophysical Impact on Structural Stability},
url = {https://www.mdpi.com/1999-4915/17/3/402},
doi = {https://doi.org/10.3390/v17030402},
year = {2025},
date = {2025-03-12},
journal = {Viruses},
volume = {17},
issue = {3},
pages = {402},
abstract = {The main protease (Mpro or 3CLpro or nsp5) of SARS-CoV-2 is crucial to the life cycle and pathogenesis of SARS-CoV-2, making it an attractive drug target to develop antivirals. This study employed the virtual screening of a few phytochemicals, and the resultant best compound, Scopoletin, was further investigated by a FRET-based enzymatic assay, revealing an experimental IC50 of 15.75 µM. The impact of Scopoletin on Mpro was further investigated by biophysical and MD simulation studies. Fluorescence spectroscopy identified a strong binding constant of 3.17 × 104 M⁻1 for Scopoletin binding to Mpro, as demonstrated by its effective fluorescence quenching of Mpro. Additionally, CD spectroscopy showed a significant reduction in the helical content of Mpro upon interaction with Scopoletin. The findings of thermodynamic measurements using isothermal titration calorimetry (ITC) supported the spectroscopic data, indicating a tight binding of Scopoletin to Mpro with a KA of 2.36 × 103 M−1. Similarly, interaction studies have also revealed that Scopoletin forms hydrogen bonds with the amino acids nearest to the active site, and this has been further supported by molecular dynamics simulation studies. These findings indicate that Scopoletin may be developed as a potential antiviral treatment for SARS-CoV-2 by targeting Mpro.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The main protease (Mpro or 3CLpro or nsp5) of SARS-CoV-2 is crucial to the life cycle and pathogenesis of SARS-CoV-2, making it an attractive drug target to develop antivirals. This study employed the virtual screening of a few phytochemicals, and the resultant best compound, Scopoletin, was further investigated by a FRET-based enzymatic assay, revealing an experimental IC50 of 15.75 µM. The impact of Scopoletin on Mpro was further investigated by biophysical and MD simulation studies. Fluorescence spectroscopy identified a strong binding constant of 3.17 × 104 M⁻1 for Scopoletin binding to Mpro, as demonstrated by its effective fluorescence quenching of Mpro. Additionally, CD spectroscopy showed a significant reduction in the helical content of Mpro upon interaction with Scopoletin. The findings of thermodynamic measurements using isothermal titration calorimetry (ITC) supported the spectroscopic data, indicating a tight binding of Scopoletin to Mpro with a KA of 2.36 × 103 M−1. Similarly, interaction studies have also revealed that Scopoletin forms hydrogen bonds with the amino acids nearest to the active site, and this has been further supported by molecular dynamics simulation studies. These findings indicate that Scopoletin may be developed as a potential antiviral treatment for SARS-CoV-2 by targeting Mpro.
Arunabh Choudhury Sneh Prabha, Asimul Islam
Understanding of Alzheimer's Disease Pathophysiology for Therapeutic Implications of Natural Products as Neuroprotective Agents Journal Article
In: Ageing Research Reviews, vol. 105, pp. 102680, 2025, ISSN: 1568-1637.
@article{Prabha2025,
title = {Understanding of Alzheimer's Disease Pathophysiology for Therapeutic Implications of Natural Products as Neuroprotective Agents},
author = {Sneh Prabha, Arunabh Choudhury, Asimul Islam, Sonu Chand Thakur, Md. Imtaiyaz Hassan},
doi = {https://doi.org/10.1016/j.arr.2025.102680},
issn = {1568-1637},
year = {2025},
date = {2025-02-06},
urldate = {2025-02-06},
journal = { Ageing Research Reviews},
volume = {105},
pages = {102680},
abstract = {Alzheimer’s disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years. Due to progressive cholinergic neuronal loss and modulation in the PKC/MAPK pathway, β-secretase gets upregulated, leading to Aβ aggregation, which further activates tau kinases that form neurofibrillary tangles (NFT). Simultaneously, antioxidant enzymes are also upregulated, increasing oxidative stress (OS) and reactive species by impairing mitochondrial function, leading to DNA damage and cell death. This review discusses the classifications and components of several natural products (NPs) that target these signaling pathways for AD treatment. NPs, including alkaloids, polyphenols, flavonoids, polysaccharides, steroids, fatty acids, tannins, and polypeptides derived from plants, microbes, marine animals, venoms, insects, and mushrooms, are explored in detail. A synergistic combination of plant metabolites, together with prebiotics and probiotics has been shown to decrease Aβ aggregates by increasing the production of bioactive compounds. Toxins derived from venomous organisms have demonstrated effectiveness in modulating signaling pathways and reducing OS. Marine metabolites have also shown neuroprotective and anti-inflammatory properties. The cholera toxin B subunit and an Aβ15 fragment have been combined to create a possible oral AD vaccine, that showed enhancement of cognitive function in mice. Insect tea is also a reliable source of antioxidants. A functional edible mushroom snack bar showed an increment in cognitive markers. Future directions and therapeutic approaches for the treatment of AD can be improved by focusing more on NPs derived from these sources.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alzheimer’s disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years. Due to progressive cholinergic neuronal loss and modulation in the PKC/MAPK pathway, β-secretase gets upregulated, leading to Aβ aggregation, which further activates tau kinases that form neurofibrillary tangles (NFT). Simultaneously, antioxidant enzymes are also upregulated, increasing oxidative stress (OS) and reactive species by impairing mitochondrial function, leading to DNA damage and cell death. This review discusses the classifications and components of several natural products (NPs) that target these signaling pathways for AD treatment. NPs, including alkaloids, polyphenols, flavonoids, polysaccharides, steroids, fatty acids, tannins, and polypeptides derived from plants, microbes, marine animals, venoms, insects, and mushrooms, are explored in detail. A synergistic combination of plant metabolites, together with prebiotics and probiotics has been shown to decrease Aβ aggregates by increasing the production of bioactive compounds. Toxins derived from venomous organisms have demonstrated effectiveness in modulating signaling pathways and reducing OS. Marine metabolites have also shown neuroprotective and anti-inflammatory properties. The cholera toxin B subunit and an Aβ15 fragment have been combined to create a possible oral AD vaccine, that showed enhancement of cognitive function in mice. Insect tea is also a reliable source of antioxidants. A functional edible mushroom snack bar showed an increment in cognitive markers. Future directions and therapeutic approaches for the treatment of AD can be improved by focusing more on NPs derived from these sources.
Iram Faiza, Ayesha
Unraveling the catalase dynamics: Biophysical and computational insights into co-solutes driven stabilization under extreme pH conditions Journal Article
In: International Journal of Biological Macromolecules, vol. 301, pp. 140467, 2025, ISSN: 0141-8130.
@article{Iram2025,
title = {Unraveling the catalase dynamics: Biophysical and computational insights into co-solutes driven stabilization under extreme pH conditions},
author = {Faiza, Iram, Ayesha, Aiman, Deepanshi, Vijh, Mohammad, Shahid, Tanzeel, Khan, Gourav, Choudhir, Tanzeel, Khan, Danish, Alam, Md. Imtaiyaz, Hassan, Asimul, Islam*},
doi = {https://doi.org/10.1016/j.ijbiomac.2025.140467},
issn = {0141-8130},
year = {2025},
date = {2025-01-28},
urldate = {2025-01-28},
journal = { International Journal of Biological Macromolecules},
volume = {301},
pages = {140467},
abstract = {Catalase plays a vital role in eliminating toxic peroxides from the human body and the environment. The versatile applications of this enzyme extend across biotechnological industries and innovative bioremediation approaches. Nonetheless, ensuring enzyme stability is a challenging task. This study investigated the efficacy of co-solutes (glucose and dextran 70) as stabilizing agents for catalase under denaturing pH conditions by employing a combination of spectroscopic techniques (UV‐visible, circular dichroism, and Trp fluorescence), calorimetric measurements (DSC and ITC), enzymatic assay, and in silico studies. The results of spectroscopic and thermal stability studies indicated that the co-solutes tend to stabilize catalase, even under extreme pH conditions. Molecular docking and ITC findings showed that glucose has a higher binding tendency to catalase than dextran 70. MD simulations further underscore reduced structural deviations (RMSF and RMSD), compact structure (Rg and SASA), and formation of H-bonds between catalase and co-solutes, complementing the in vitro observations. This study contributes to the understanding of enzyme stability under suboptimal pH conditions and paves the way for the development of more robust enzyme formulations suitable for a range of applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Catalase plays a vital role in eliminating toxic peroxides from the human body and the environment. The versatile applications of this enzyme extend across biotechnological industries and innovative bioremediation approaches. Nonetheless, ensuring enzyme stability is a challenging task. This study investigated the efficacy of co-solutes (glucose and dextran 70) as stabilizing agents for catalase under denaturing pH conditions by employing a combination of spectroscopic techniques (UV‐visible, circular dichroism, and Trp fluorescence), calorimetric measurements (DSC and ITC), enzymatic assay, and in silico studies. The results of spectroscopic and thermal stability studies indicated that the co-solutes tend to stabilize catalase, even under extreme pH conditions. Molecular docking and ITC findings showed that glucose has a higher binding tendency to catalase than dextran 70. MD simulations further underscore reduced structural deviations (RMSF and RMSD), compact structure (Rg and SASA), and formation of H-bonds between catalase and co-solutes, complementing the in vitro observations. This study contributes to the understanding of enzyme stability under suboptimal pH conditions and paves the way for the development of more robust enzyme formulations suitable for a range of applications.
2024
Prithvi Singh Mohammad Masood, Daaniyal Harris
Nitric oxide as a double-edged sword in pulmonary viral infections: Mechanistic insights and potential therapeutic implications Journal Article
In: Gene, vol. 899, iss. 148148, 2024.
@article{nokey,
title = {Nitric oxide as a double-edged sword in pulmonary viral infections: Mechanistic insights and potential therapeutic implications},
author = {Mohammad Masood, Prithvi Singh, Daaniyal Harris, Faizya Khan, Daraksha Yameen, Seerat Siraj, Asimul Islam, Ravins Dohare, Mohammad Mahfuzul Haque},
doi = {https://doi.org/10.1016/j.gene.2024.148148},
year = {2024},
date = {2024-03-20},
urldate = {2024-03-20},
journal = {Gene},
volume = {899},
issue = {148148},
abstract = {In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10–9) regulation of guanylate cyclase activity (p-value = 7.5 x 10–12), arginine binding (p-value = 2.62 x 10–11), vesicle membrane (p-value = 3.93 x 10–8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10–9) regulation of guanylate cyclase activity (p-value = 7.5 x 10–12), arginine binding (p-value = 2.62 x 10–11), vesicle membrane (p-value = 3.93 x 10–8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.
Rashid Waseem Tanzeel Khan, Mohammad Shahid; Islam, Asimul
Understanding the Modulation of α-Synuclein Fibrillation by N-Acetyl Aspartate: A Brain Metabolite Journal Article
In: ACS Omega, vol. 9, pp. 12262-122771, 2024.
@article{Khan0000,
title = {Understanding the Modulation of α-Synuclein Fibrillation by N-Acetyl Aspartate: A Brain Metabolite},
author = {Tanzeel Khan, Rashid Waseem, Mohammad Shahid, Jaoud Ansari, Md. Imtaiyaz Hassan, Anash Shamsi, and Asimul Islam},
doi = {https://doi.org/10.1021/acsomega.4c00595},
year = {2024},
date = {2024-02-29},
urldate = {2024-02-29},
journal = {ACS Omega},
volume = {9},
pages = {12262-122771},
abstract = {α-Synuclein (α-Syn) fibrillation is a prominent contributor to neuronal deterioration and plays a significant role in the advancement of Parkinson’s Disease (PD). Considering this, the exploration of novel compounds that can inhibit or modulate the aggregation of α-Syn is a topic of significant research. This study, for the first time, elucidated the effect of N-acetyl aspartate (NAA), a brain osmolyte, on α-Syn aggregation using spectroscopic and microscopic approaches. Thioflavin T (ThT) assay revealed that a lower concentration of NAA inhibits α-Syn aggregation, whereas higher concentrations of NAA accelerate the aggregation. Further, this paradoxical effect of NAA was complemented by ANS, RLS, and the turbidity assay. The secondary structure transition was more pronounced at higher concentrations of NAA by circular dichroism, corroborating the fluorescence spectroscopic observations. Confocal microscopy also confirmed the paradoxical effect of NAA on α-Syn aggregation. Interaction studies including fluorescence quenching and molecular docking were employed to determine the binding affinity and critical residues involved in the α-Syn-NAA interaction. The explanation for this paradoxical nature of NAA could be a solvophobic effect. The results offer a profound understanding of the modulatory mechanism of α-Syn aggregation by NAA, thereby suggesting the potential role of NAA at lower concentrations in therapeutics against α-Syn aggregation-related disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
α-Synuclein (α-Syn) fibrillation is a prominent contributor to neuronal deterioration and plays a significant role in the advancement of Parkinson’s Disease (PD). Considering this, the exploration of novel compounds that can inhibit or modulate the aggregation of α-Syn is a topic of significant research. This study, for the first time, elucidated the effect of N-acetyl aspartate (NAA), a brain osmolyte, on α-Syn aggregation using spectroscopic and microscopic approaches. Thioflavin T (ThT) assay revealed that a lower concentration of NAA inhibits α-Syn aggregation, whereas higher concentrations of NAA accelerate the aggregation. Further, this paradoxical effect of NAA was complemented by ANS, RLS, and the turbidity assay. The secondary structure transition was more pronounced at higher concentrations of NAA by circular dichroism, corroborating the fluorescence spectroscopic observations. Confocal microscopy also confirmed the paradoxical effect of NAA on α-Syn aggregation. Interaction studies including fluorescence quenching and molecular docking were employed to determine the binding affinity and critical residues involved in the α-Syn-NAA interaction. The explanation for this paradoxical nature of NAA could be a solvophobic effect. The results offer a profound understanding of the modulatory mechanism of α-Syn aggregation by NAA, thereby suggesting the potential role of NAA at lower concentrations in therapeutics against α-Syn aggregation-related disorders.
Arunabh Choudhury Saleha Anwar, Afzal Hussain
Harnessing memantine in Alzheimer's disease therapy through inhibition of microtubule affinity-regulating kinase: Mechanistic insights Journal Article
In: International Journal of Biological Macromolecules, vol. 262, iss. Part 2, no. 130090, 2024.
@article{Anwar2024,
title = {Harnessing memantine in Alzheimer's disease therapy through inhibition of microtubule affinity-regulating kinase: Mechanistic insights},
author = {Saleha Anwar, Arunabh Choudhury, Afzal Hussain, Mohamed F. AlAjmi, Md. Imtaiyaz Hassan, Asimul Islam},
doi = {https://doi.org/10.1016/j.ijbiomac.2024.130090},
year = {2024},
date = {2024-02-09},
urldate = {2024-02-09},
journal = {International Journal of Biological Macromolecules},
volume = {262},
number = {130090},
issue = {Part 2},
abstract = {Alzheimer's disease (AD) is one of the neurodegenerative disorder that primarily affects memory, thinking, and behavior, eventually leading to severe cognitive impairment. Therapeutic management of AD is urgently needed to improve the quality and lifestyle of patients. Tau phosphorylating kinases are considered attractive therapeutic targets. Microtubule affinity-regulating kinase 4 (MARK4) is directly linked with pathological phosphorylations of tau, highlighting its role in the therapeutic targeting of AD. The current manuscript shows the MARK4 inhibitory effect of Memantine (MEM), a drug used in treating AD. We have performed fluorescence based binding measurements, enzyme inhibition assay, docking and molecular dynamics (MD) simulations to understand the binding of of MARK4 and MEM and subsequent inhibition in the kinase activity. A 100 ns MD simulations provided a detailed analysis of MARK4-MEM complex and the role of potential critical residues in the binding. Finally, this study provides molecular insights into the therapeutic implication of MEM in AD therapeutics. We propose MEM effectively inhibits MARK4, it may be implicated in the development of targeted and efficient treatments for AD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alzheimer's disease (AD) is one of the neurodegenerative disorder that primarily affects memory, thinking, and behavior, eventually leading to severe cognitive impairment. Therapeutic management of AD is urgently needed to improve the quality and lifestyle of patients. Tau phosphorylating kinases are considered attractive therapeutic targets. Microtubule affinity-regulating kinase 4 (MARK4) is directly linked with pathological phosphorylations of tau, highlighting its role in the therapeutic targeting of AD. The current manuscript shows the MARK4 inhibitory effect of Memantine (MEM), a drug used in treating AD. We have performed fluorescence based binding measurements, enzyme inhibition assay, docking and molecular dynamics (MD) simulations to understand the binding of of MARK4 and MEM and subsequent inhibition in the kinase activity. A 100 ns MD simulations provided a detailed analysis of MARK4-MEM complex and the role of potential critical residues in the binding. Finally, this study provides molecular insights into the therapeutic implication of MEM in AD therapeutics. We propose MEM effectively inhibits MARK4, it may be implicated in the development of targeted and efficient treatments for AD.
Ghulam Md Ashraf Ishfaq A Ahanger, Anurag Sharma
Comprehensive perspective towards the management of proteinopathies by elucidating protein misfolding and aggregation Journal Article
In: CNS & Neurological Disorders-Drug Targets-CNS & Neurological Disorders), vol. 23, iss. 2, pp. 153-180, 2024.
@article{Ahanger2024,
title = {Comprehensive perspective towards the management of proteinopathies by elucidating protein misfolding and aggregation},
author = {Ishfaq A Ahanger, Ghulam Md Ashraf, Anurag Sharma, Asimul Islam},
doi = {https://doi.org/10.2174/1871527322666230306085937},
year = {2024},
date = {2024-02-02},
urldate = {2024-02-02},
journal = {CNS & Neurological Disorders-Drug Targets-CNS & Neurological Disorders)},
volume = {23},
issue = {2},
pages = {153-180},
abstract = {Protein misfolding and aggregation is the phenomenon of the generic propensity of proteins, considered as a dark side of the protein world, and its exact mechanism is still not deciphered. Understanding the complexity of protein aggregation is currently the primary apprehension and challenge in biology and medicine due to their association with various debilitating human proteinopathies and neurodegenerative diseases. The mechanism of protein aggregation, associated diseases, and the development of efficient therapeutic strategies against these diseases are very challenging. These diseases are caused by different proteins, each protein with different mechanisms and consisting of various microscopic phases or events. These microscopic steps are functioning on different timescales during aggregation. Here, we highlighted the different features and current trends in protein aggregation. The study thoroughly recapitulates the various factors influencing, possible causes, types of aggregates and aggregation, their different proposed mechanisms, and the methods used to study the aggregation. Additionally, the formation and elimination of misfolded or aggregated proteins in the cell, the role of the ruggedness of the protein folding landscape in protein aggregation, proteinopathies, and the challenges for their prevention are comprehensively elucidated. A holistic understanding of different aspects of aggregation, molecular steps governing the various features of protein quality control, and crucial queries about the modulation of these processes and their interactions with other systems in cellular protein quality control can be considered conducive to comprehending the mechanism, designing effective approaches towards prevention of protein aggregation, rationalizing the etiology and development of novel strategies against therapy and management of the proteinopathies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Protein misfolding and aggregation is the phenomenon of the generic propensity of proteins, considered as a dark side of the protein world, and its exact mechanism is still not deciphered. Understanding the complexity of protein aggregation is currently the primary apprehension and challenge in biology and medicine due to their association with various debilitating human proteinopathies and neurodegenerative diseases. The mechanism of protein aggregation, associated diseases, and the development of efficient therapeutic strategies against these diseases are very challenging. These diseases are caused by different proteins, each protein with different mechanisms and consisting of various microscopic phases or events. These microscopic steps are functioning on different timescales during aggregation. Here, we highlighted the different features and current trends in protein aggregation. The study thoroughly recapitulates the various factors influencing, possible causes, types of aggregates and aggregation, their different proposed mechanisms, and the methods used to study the aggregation. Additionally, the formation and elimination of misfolded or aggregated proteins in the cell, the role of the ruggedness of the protein folding landscape in protein aggregation, proteinopathies, and the challenges for their prevention are comprehensively elucidated. A holistic understanding of different aspects of aggregation, molecular steps governing the various features of protein quality control, and crucial queries about the modulation of these processes and their interactions with other systems in cellular protein quality control can be considered conducive to comprehending the mechanism, designing effective approaches towards prevention of protein aggregation, rationalizing the etiology and development of novel strategies against therapy and management of the proteinopathies.
Afreen Khan Aanchal Rathi, Shaista Haider
Exploring the potential of baicalin and resveratrol as PIM-1 kinase inhibitors: Therapeutic targeting of prostate and breast cancers Journal Article
In: Journal of Molecular Liquids, vol. 396, iss. 124026, 2024.
@article{Rathi2024,
title = {Exploring the potential of baicalin and resveratrol as PIM-1 kinase inhibitors: Therapeutic targeting of prostate and breast cancers},
author = {Aanchal Rathi, Afreen Khan, Shaista Haider, Sonam Roy, Aaliya Taiyab, Shivam Mahendru, Afzal Hussain, Anindita Chakrabarty, Asimul Islam, Md. Imtaiyaz Hassan, Mohammad Mahfuzul Haque},
doi = {https://doi.org/10.1016/j.molliq.2024.124026},
year = {2024},
date = {2024-01-22},
urldate = {2024-01-22},
journal = {Journal of Molecular Liquids},
volume = {396},
issue = {124026},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2023
Daraksha Yameen Seerat Siraj, Shivani Bhati
Sugar osmolyte inhibits and attenuates the fibrillogenesis in RNase A: An in vitro and in silico characterizations Journal Article
In: International Journal of Biological Macromolecules, vol. 253, iss. Part 8, pp. 127378, 2023.
@article{,
title = {Sugar osmolyte inhibits and attenuates the fibrillogenesis in RNase A: An in vitro and in silico characterizations},
author = {Seerat Siraj, Daraksha Yameen, Shivani Bhati, Teeba Athar, Salman Khan, Jaydeep Bhattacharya, Asimul Islam, Mohammad Mahfuzul Haque},
doi = {https://doi.org/10.1016/j.ijbiomac.2024.130090},
year = {2023},
date = {2023-12-31},
urldate = {2024-02-09},
journal = {International Journal of Biological Macromolecules},
volume = {253},
issue = {Part 8},
pages = {127378},
abstract = {Mechanisms of protein aggregation are of immense interest in therapeutic biology and neurodegenerative medicine. Biochemical processes within the living cell occur in a highly crowded environment. The phenomenon of macromolecular crowding affects the diffusional and conformational dynamics of proteins and modulates their folding. Macromolecular crowding is reported to cause protein aggregation in some cases, so it is a cause of concern as it leads to a plethora of neurodegenerative disorders and systemic amyloidosis. To divulge the mechanism of aggregation, it is imperative to study aggregation in well-characterized model proteins in the presence of macromolecular crowder. One such protein is ribonuclease A (RNase A), which deciphers neurotoxic function in humans; therefore we decided to explore the amyloid fibrillogenesis of this thermodynamically stable protein. To elucidate the impact of crowder, dextran-70 and its monomer glucose on the aggregation profile of RNase-A various techniques such as Absorbance, Fluorescence, Fourier Transforms Infrared, Dynamic Light Scattering and circular Dichroism spectroscopies along with imaging techniques like Atomic Force Microscopy and Transmission Electron Microscopy were employed. Thermal aggregation and fibrillation were further promoted by dextran-70 while glucose counteracted the effect of the crowding agent in a concentration-dependent manner. This study shows that glucose provides stability to the protein and prevents fibrillation. Intending to combat aggregation, which is the hallmark of numerous late-onset neurological disorders and systemic amyloidosis, this investigation unveils that naturally occurring osmolytes or other co-solutes can be further exploited in novel drug design strategies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mechanisms of protein aggregation are of immense interest in therapeutic biology and neurodegenerative medicine. Biochemical processes within the living cell occur in a highly crowded environment. The phenomenon of macromolecular crowding affects the diffusional and conformational dynamics of proteins and modulates their folding. Macromolecular crowding is reported to cause protein aggregation in some cases, so it is a cause of concern as it leads to a plethora of neurodegenerative disorders and systemic amyloidosis. To divulge the mechanism of aggregation, it is imperative to study aggregation in well-characterized model proteins in the presence of macromolecular crowder. One such protein is ribonuclease A (RNase A), which deciphers neurotoxic function in humans; therefore we decided to explore the amyloid fibrillogenesis of this thermodynamically stable protein. To elucidate the impact of crowder, dextran-70 and its monomer glucose on the aggregation profile of RNase-A various techniques such as Absorbance, Fluorescence, Fourier Transforms Infrared, Dynamic Light Scattering and circular Dichroism spectroscopies along with imaging techniques like Atomic Force Microscopy and Transmission Electron Microscopy were employed. Thermal aggregation and fibrillation were further promoted by dextran-70 while glucose counteracted the effect of the crowding agent in a concentration-dependent manner. This study shows that glucose provides stability to the protein and prevents fibrillation. Intending to combat aggregation, which is the hallmark of numerous late-onset neurological disorders and systemic amyloidosis, this investigation unveils that naturally occurring osmolytes or other co-solutes can be further exploited in novel drug design strategies.
Arunabh Choudhury Saba Noor, Ali Raza
Probing Baicalin as potential inhibitor of Aurora kinase B: a step towards lung cancer therapy Journal Article
In: International Journal of Biological Macromolecules, vol. 258, iss. 128813, 2023.
@article{nokey,
title = {Probing Baicalin as potential inhibitor of Aurora kinase B: a step towards lung cancer therapy},
author = {Saba Noor, Arunabh Choudhury, Ali Raza, Anam Ashraf, Khursheed Ul Islam, Afzal Hussain, Khadija Imtiyaz, Asimul Islam, Md Imtaiyaz Hassan},
doi = {https://doi.org/10.1016/j.ijbiomac.2023.128813},
year = {2023},
date = {2023-12-18},
urldate = {2023-12-18},
journal = {International Journal of Biological Macromolecules},
volume = {258},
issue = {128813},
abstract = {Cell cycle regulators play pivotal roles as their dysregulation, leads to atypical proliferation and intrinsic genomic instability in cancer cells. Abnormal expression and functioning of Aurora kinase B (AURKB) are associated with cancer pathogenesis and thus exploited as a potential therapeutic target for the development of anti-cancer therapeutics. To identify effective AURKB inhibitors, a series of polyphenols was investigated to check their potential to inhibit recombinant AURKB. Their binding affinities were experimentally validated through fluorescence binding studies. Enzyme inhibition assay revealed that Mangiferin and Baicalin significantly inhibited AURKB activity with an IC50 values of 20.0 μM and 31.1 μM, respectively. To get atomistic insights into the binding mechanism, molecular docking and MD simulations of 100 ns were performed. Both compounds formed many non-covalent interactions with the residues of the active site pocket of AURKB. In addition, minimal conformational changes in the structure and formation of stable AURKB-ligand complex were observed during MD simulation analysis. Finally, cell-based studies suggested that Baicalin exhibited in-vitro cytotoxicity and anti-proliferative effects on lung cancer cell lines. Conclusively, Baicalin may be considered a promising therapeutic molecule against AURKB, adding an additional novel lead to the anti-cancer repertoire.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cell cycle regulators play pivotal roles as their dysregulation, leads to atypical proliferation and intrinsic genomic instability in cancer cells. Abnormal expression and functioning of Aurora kinase B (AURKB) are associated with cancer pathogenesis and thus exploited as a potential therapeutic target for the development of anti-cancer therapeutics. To identify effective AURKB inhibitors, a series of polyphenols was investigated to check their potential to inhibit recombinant AURKB. Their binding affinities were experimentally validated through fluorescence binding studies. Enzyme inhibition assay revealed that Mangiferin and Baicalin significantly inhibited AURKB activity with an IC50 values of 20.0 μM and 31.1 μM, respectively. To get atomistic insights into the binding mechanism, molecular docking and MD simulations of 100 ns were performed. Both compounds formed many non-covalent interactions with the residues of the active site pocket of AURKB. In addition, minimal conformational changes in the structure and formation of stable AURKB-ligand complex were observed during MD simulation analysis. Finally, cell-based studies suggested that Baicalin exhibited in-vitro cytotoxicity and anti-proliferative effects on lung cancer cell lines. Conclusively, Baicalin may be considered a promising therapeutic molecule against AURKB, adding an additional novel lead to the anti-cancer repertoire.
Pradakshina Sharma Khadega Khamis Moh Alazoumi, Asimul Islam
Mitigation of the Deleterious Effect of Heavy Metals on the Conformational Stability of Ubiquitin through Osmoprotectants Journal Article
In: Cell Biochemistry and Biophysics, vol. 82, pp. 193-202, 2023, (Alazoumi, K.K.M., Sharma, P., Islam, A. et al. Mitigation of the Deleterious Effect of Heavy Metals on the Conformational Stability of Ubiquitin through Osmoprotectants. Cell Biochem Biophys 82, 193–202 (2024). https://doi.org/10.1007/s12013-023-01188-3).
@article{Alazoumi2023,
title = {Mitigation of the Deleterious Effect of Heavy Metals on the Conformational Stability of Ubiquitin through Osmoprotectants},
author = {Khadega Khamis Moh Alazoumi, Pradakshina Sharma, Asimul Islam, Humaira Farooqi},
doi = {https://doi.org/10.1007/s12013-023-01188-3},
year = {2023},
date = {2023-10-16},
urldate = {2023-10-16},
journal = {Cell Biochemistry and Biophysics},
volume = {82},
pages = {193-202},
abstract = {The Ubiquitin-Proteasome System (UPS) is important in protein homeostasis and is involved in many cell processes. UPS’s wide range of regulatory activities is based on the unique and diverse signals transmitted through all-encompassing processes. Cells need a fully functional UPP to cope with oxidative stress, so cellular redox status modulates ubiquitin activity. However, these protein quality control systems are compromised under adverse conditions such as heavy metal stress, resulting in pathological conditions. Heavy metals disrupt the physiological action of sensitive proteins by forming complexes with side-chain functional groups or by dislocating critical metal ions in metalloproteins. In addition, perturbation in the structure of Ubiquitin may affect the ubiquitin-proteasome pathway. In this study, it has been investigated the effects of heavy metals likewise chromium (Cr), cadmium (Cd), and mercury chloride (HgCl2) on the conformational stability of Ubiquitin as well as overcome their hazardous effect, the interaction of osmo-protectants such as Sesamol, gallic acid, Glycine, and ascorbic acid have also been explored in the study. The near and far UV-circular dichroism measurements deduced the secondary and tertiary structural changes. The size of the Ubiquitin before and after exposure to heavy metals was measured by DLS (dynamic light scattering). Docking research was also used to investigate the interaction of Ubiquitin with various heavy metals. Near and far UV-circular dichroism (CD) measurements revealed that mercury, chromium, and cadmium disrupt Ubiquitin’s secondary and tertiary structure. The effect of chromium, even at low concentrations, was significantly deleterious compared to cadmium and mercury chloride. Ubiquitin’s far-UV circular dichroism spectra subjected to heavy metals were recorded in several osmo-protectants, such as ascorbic acid, Glycine, gallic acid, and Sesamol, which offset the adverse effects of heavy metals. DLS studies revealed a noteworthy change in the hydrodynamic radius of Ubiquitin in the presence of heavy metals. Docking analysis revealed a significant binding affinity of mercury and cadmium ions with Ubiquitin. This study can infer the heavy metals’ disruption of Ubiquitin’s secondary and tertiary structure. Osmo-protectants produced by animal cells are more effective against heavy metals than plant antioxidants.},
note = {Alazoumi, K.K.M., Sharma, P., Islam, A. et al. Mitigation of the Deleterious Effect of Heavy Metals on the Conformational Stability of Ubiquitin through Osmoprotectants. Cell Biochem Biophys 82, 193–202 (2024). https://doi.org/10.1007/s12013-023-01188-3},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Ubiquitin-Proteasome System (UPS) is important in protein homeostasis and is involved in many cell processes. UPS’s wide range of regulatory activities is based on the unique and diverse signals transmitted through all-encompassing processes. Cells need a fully functional UPP to cope with oxidative stress, so cellular redox status modulates ubiquitin activity. However, these protein quality control systems are compromised under adverse conditions such as heavy metal stress, resulting in pathological conditions. Heavy metals disrupt the physiological action of sensitive proteins by forming complexes with side-chain functional groups or by dislocating critical metal ions in metalloproteins. In addition, perturbation in the structure of Ubiquitin may affect the ubiquitin-proteasome pathway. In this study, it has been investigated the effects of heavy metals likewise chromium (Cr), cadmium (Cd), and mercury chloride (HgCl2) on the conformational stability of Ubiquitin as well as overcome their hazardous effect, the interaction of osmo-protectants such as Sesamol, gallic acid, Glycine, and ascorbic acid have also been explored in the study. The near and far UV-circular dichroism measurements deduced the secondary and tertiary structural changes. The size of the Ubiquitin before and after exposure to heavy metals was measured by DLS (dynamic light scattering). Docking research was also used to investigate the interaction of Ubiquitin with various heavy metals. Near and far UV-circular dichroism (CD) measurements revealed that mercury, chromium, and cadmium disrupt Ubiquitin’s secondary and tertiary structure. The effect of chromium, even at low concentrations, was significantly deleterious compared to cadmium and mercury chloride. Ubiquitin’s far-UV circular dichroism spectra subjected to heavy metals were recorded in several osmo-protectants, such as ascorbic acid, Glycine, gallic acid, and Sesamol, which offset the adverse effects of heavy metals. DLS studies revealed a noteworthy change in the hydrodynamic radius of Ubiquitin in the presence of heavy metals. Docking analysis revealed a significant binding affinity of mercury and cadmium ions with Ubiquitin. This study can infer the heavy metals’ disruption of Ubiquitin’s secondary and tertiary structure. Osmo-protectants produced by animal cells are more effective against heavy metals than plant antioxidants.
2022
Anas Shamsi Rashid Waseem, Mohd Shahbaz
Effect of pH on the structure and stability of irisin, a multifunctional protein: Multispectroscopic and molecular dynamics simulation approach Journal Article
In: Journal of Molecular Structure, vol. 1252, pp. 132141, 2022, ISSN: 0022-2860.
@article{Waseem2022,
title = {Effect of pH on the structure and stability of irisin, a multifunctional protein: Multispectroscopic and molecular dynamics simulation approach},
author = {Rashid Waseem, Anas Shamsi, Mohd Shahbaz, Tanzeel Khan, Syed Naqui Kazin, Faizan Ahmad, Md. Imtaiyaz Hassan, Asimul Islam},
url = {https://academia.edu/keypass/aDc3SXhKVWZTeHRSNE9jWmtjRHhhMm94aG5ETFFvYW9hRy9KSnZWTHJ3ST0tLVZOZlROS0xmL1RvSlFaOXFWWmFhZXc9PQ==-5b6e9b3de6eb2c8cbdca5946d4e4fbe5c740afa4/t/c00AD-SzwSAsB-zL8Tp/ai_podcast/114830160},
doi = {https://doi.org/10.1016/j.molstruc.2021.132141},
issn = {0022-2860},
year = {2022},
date = {2022-03-15},
urldate = {2022-03-15},
journal = {Journal of Molecular Structure},
volume = {1252},
pages = {132141},
abstract = {Irisin is a potential therapeutic agent to prevent or treat various metabolic-related disorders and neurodegenerative diseases viz. Alzheimer's disease (AD). In this study, we have employed a multispectroscopic approach to elucidate the structural and conformational changes in the irisin at varying pH (pH 2.0 to 12.0). The spectroscopic measurements revealed that irisin maintains its structure (both secondary and tertiary) in the alkaline pH range, with minimal structural changes observed across it. However, secondary and tertiary structural alterations were evident across the acidic pH range. CD spectroscopy suggested a gain of the secondary structure in the acidic pH range, implying that irisin is more stable at acidic pH, with maximum stability and compactness observed at pH 4.0. In vitro observations were further validated by in silico studies. Molecular dynamics simulation also suggested that irisin assumes higher stability in the conformational space at pH 4.0 and 6.0 than the rest of the system. This study can serve as a platform to delineate the enhanced functionality of irisin at lower pH that can be implicated in developing therapies for metabolic disorders, including diabetes and obesity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Irisin is a potential therapeutic agent to prevent or treat various metabolic-related disorders and neurodegenerative diseases viz. Alzheimer's disease (AD). In this study, we have employed a multispectroscopic approach to elucidate the structural and conformational changes in the irisin at varying pH (pH 2.0 to 12.0). The spectroscopic measurements revealed that irisin maintains its structure (both secondary and tertiary) in the alkaline pH range, with minimal structural changes observed across it. However, secondary and tertiary structural alterations were evident across the acidic pH range. CD spectroscopy suggested a gain of the secondary structure in the acidic pH range, implying that irisin is more stable at acidic pH, with maximum stability and compactness observed at pH 4.0. In vitro observations were further validated by in silico studies. Molecular dynamics simulation also suggested that irisin assumes higher stability in the conformational space at pH 4.0 and 6.0 than the rest of the system. This study can serve as a platform to delineate the enhanced functionality of irisin at lower pH that can be implicated in developing therapies for metabolic disorders, including diabetes and obesity.
2021
Ali Nabeel, Amna
Parkinson’s Disease: A Current Perspectives on Parkinson’s Disease and Key Bioactive Natural Compounds as Future Potential Drug Candidates Journal Article
In: Current Drug Targets, vol. 23, iss. 1, pp. 2-20, 2021, ISSN: 1873-5592.
@article{Ali2021,
title = {Parkinson’s Disease: A Current Perspectives on Parkinson’s Disease and Key Bioactive Natural Compounds as Future Potential Drug Candidates},
author = {Nabeel, Ali, Amna, Syeda, Tenzin, Topgyal, Naseem, Gaur, Asimul, Islam*},
doi = {http://dx.doi.org/10.2174/1389450122666210623115505},
issn = {1873-5592},
year = {2021},
date = {2021-06-23},
urldate = {2021-06-23},
journal = {Current Drug Targets},
volume = {23},
issue = {1},
pages = {2-20},
abstract = {Parkinson’s disease (PD) is one of the most common types of neurological disorder prevailing worldwide and is rapidly increasing in the elderly population across the globe. The cause of PD is still unknown, but a number of genetic as well as environmental factors contributing to the pathogenesis of Parkinson’s disease have been identified. The hallmark of PD includes dopamine deficiency (neurotransmitter imbalance) due to the gradual loss of dopaminergic nerves in the substantia nigra in the midbrain. Studying the mutation of associated genes is particularly informative in understanding the fundamental molecular and pathogenic changes in PD. Intracellular accumulation of misfolded or degraded protein due to mutated genes leading to the manifestation of mitochondrial dysfunction, oxidative stress followed by multifaceted patho-physiologic symptoms. Other studies include the appearance of both motor and non-motor responses like resting tremor, muscle stiffness, slow movement and anxiety, anaemia, constipation, rapid eye movement sleep behaviour disorder. Many bioactive natural compounds have shown positive pharmacological results in treating a number of extensive disease models of PD. Despite the availability of end number of potent medicinal plants around the world, limited research has been done associated with various neurological disorders, including PD. The currently available dopamine-based drug treatments have several side-effects, further, not effective enough to combat PD completely. Therefore, various plant-based compounds with medicinal benefits have grabbed lots of attention of researchers to deal with various life-threatening neurodegenerative disorders like PD. On the basis of literature available till date, here, we have discussed and addressed the molecular basis, current scenario, and the best possible treatment of PD for the future with minimal or no side-effects using various key bioactive compounds from natural origin/medicinal plants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Parkinson’s disease (PD) is one of the most common types of neurological disorder prevailing worldwide and is rapidly increasing in the elderly population across the globe. The cause of PD is still unknown, but a number of genetic as well as environmental factors contributing to the pathogenesis of Parkinson’s disease have been identified. The hallmark of PD includes dopamine deficiency (neurotransmitter imbalance) due to the gradual loss of dopaminergic nerves in the substantia nigra in the midbrain. Studying the mutation of associated genes is particularly informative in understanding the fundamental molecular and pathogenic changes in PD. Intracellular accumulation of misfolded or degraded protein due to mutated genes leading to the manifestation of mitochondrial dysfunction, oxidative stress followed by multifaceted patho-physiologic symptoms. Other studies include the appearance of both motor and non-motor responses like resting tremor, muscle stiffness, slow movement and anxiety, anaemia, constipation, rapid eye movement sleep behaviour disorder. Many bioactive natural compounds have shown positive pharmacological results in treating a number of extensive disease models of PD. Despite the availability of end number of potent medicinal plants around the world, limited research has been done associated with various neurological disorders, including PD. The currently available dopamine-based drug treatments have several side-effects, further, not effective enough to combat PD completely. Therefore, various plant-based compounds with medicinal benefits have grabbed lots of attention of researchers to deal with various life-threatening neurodegenerative disorders like PD. On the basis of literature available till date, here, we have discussed and addressed the molecular basis, current scenario, and the best possible treatment of PD for the future with minimal or no side-effects using various key bioactive compounds from natural origin/medicinal plants.