@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}