THERAPEUTICS APPLICATION OF ANTI-CANCEROUS DRUGS IN NEURODEGENERATIVE DISORDERS

Abstract

Neurodegenerative diseases (NDDs) are chronic devastating ailment manifested by selective loss of neurons associated with accumulation of altered proteins in the brain. Despite a plethora of modifications identified for different neurotoxic proteins, such as tau, amyloid-β, α-synuclein and prion protein, NDDs are classified on the basis of comprehensive and extensive evaluation of the morphological and structural features of aggregated protein deposits, and their association with clinical symptoms in the pathophysiology of disease. Compelling evidence suggests that accumulated protein deposits show a hierarchical involvement of distinct regions of brain and triggers the progression of a number of neurological disorders that have been categorized as tauopathies, TDP-43 proteinopathies and α-synucleinopathies. α-synuclein is among the center of focus to comprehend a number of NDDs involving Parkinson’s disease (PD), Dementia with Lewy bodies (DLB) and Multiple System atrophy (MSA), known as α-synucleinopathies. α-synuclein has also been found secondarily in a number of other diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Understanding how a normal α-synuclein protein forms aggregates and deposits is an important aspect in the pathophysiology of these diseases. In this work, we have focused on the toxic form of α-synuclein protein. The objective of present study is to identify potent inhibitors (ligands) 10 | P a g e which interact with the active site of toxic α-synuclein protein and inhibit its accumulation. In this study, insilico molecular docking studies was performed against α-synuclein using three plant derived compounds having anticancerous property: (a) Genistein (b) Hesperidine, and (c) Epigallocatechin-3-gallate. These compounds were analyzed using Lipinski filter, Autodock and LIGPLOT analysis tools. Further, our study revealed that Genistein was the best fit ligand against the active site of α-synuclein with minimum binding energy and inhibition constant. Finally, these natural compounds with the ability to interact with α-synuclein in silico can further be analyzed using in vitro and in vivo studies.