NEUROPROTECTIVE ROLE OF BIMOCLOMOL IN ECTOPIC CELL CYCLE IN PARKINSON'S DISEASE: NEW INSIGHTS
Keywords:Nil, Bimoclomol, Cell cycle, Heat shock proteins 70, Therapeutics
Objective: Parkinson's disease (PD) is a debilitating age-related neurodegenerative disease characterized by the canonical formation of intracellular Lewy bodies comprising Î±-synuclein protein. Despite the knowledge of factors causing PD, it remains irreversible and incurable. Recent studies have highlighted the physiological and pathological involvement of cell cycle proteins in PD. The intriguing relationship between PARK2 and cyclin E which leads to upregulation of cyclin E in the absence of functional PARK2 contributes heavily in the onset and progression of PD. The objective of this study is to explore neuroprotective action of bimoclomol in attenuating the level of cyclin E and inhibiting post-mitotic cell division led neurodegeneration in PD.
Methods: We employed various in silico methods such as drug-likeness parameters, namely, Lipinski filter analysis, Ghose parameters, Veber rules, absorption, distribution, metabolism, and excretion - toxicity analysis, pharmacophore based target prediction, active site prediction, and molecular docking studies.
Results: The binding of bimoclomol inhibited cyclin E, thereby, attenuating post-mitotic cell division led neurodegeneration in PD.
Conclusion: This study outlines the novel potential of bimoclomol in attenuating cyclin E led neuronal death in PD which may be mediated by heat shock proteins (HSP70).
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