IN SILICO ANALYSIS OF POTENTIAL DRUGS AS NEUROPROTECTANTS TARGETING MITOCHONDRIAL PROTEIN PINK1 OF PARKINSON’S DISEASE

Abstract

Parkinson’s disease (PD) is regarded as one of the most chronic as well as a persistent neurodegenerative disorder, generally affecting elderly groups, with an obscure and complicated etiology. PD has a genetic association as it is caused due to mutations in different genes and thereby alters proteins they encode like DJ-1, Parkin, etc. The hallmarks of these diseases are the aggregation of altered proteins. Herein this review, we try to incorporate upon the details underlying mitochondrial dysfunction in PD and how it can be used as a curative agent providing vital acumens into its indispensable role in PD pathogenesis and serving as a purpose for future drug development. The mitochondria assist in various cellular processes, like bioenergetics, metabolism, cell signaling, redox homeostasis, and apoptosis. Even the well-being and integrity of mitochondria, depends on how precisely the protein is imported, folded, and regulated is defined as mitochondrial protein quality control; its impairment results in mitochondrial dysfunction, which can lead to different pathophysiological outcomes and also causes commencement of diseases like many irresistible proofs indicating that disturbance in mitochondrial dynamics is one of the prime factors involved in causing PD.

PINK1 is one of the central point associating mitochondrial dysfunction to PD and which may be targeted for PD therapy. Similar compounds to an approved drug-like Amphetamine were screen to target neuroprotective role against mitochondrial dysfunction in PD model, but due to its structural complication, it has black boxed warning and can cause cardiotoxicity, thus hunt for better nontoxic potential candidates continues.

Keywords: Parkinson’s disease; Mitochondria; mitophagy; mitochondrial protein quality control; Molecular docking.