SIGNALLING MECHANISM AND THERAPEUTICS ACTION OF BIOMOLECULES IN NEURODEGENERATIVE DISORDER

Abstract

Neurodegenerative disorder (NDD) continues to traumatize an aging proportion of the human population, especially in the industrialized world. Aging has long been recognized as a compound process of damage accretion that ultimately leads to notice able disruption of multiple cellular and molecular proceedings, which ultimately are translated into various chronic ailments such as Parkinson's disease (PD), Alzheimer's disease (AD), Multiple Sclerosis (MS) and many more. Parkinson's disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders after AD. Currently, there is no cure and researchers continue to probe the therapeutic prospect of PD. Out of several factors contributing to PD prognosis, the role of p38 MAPK and PI3K/AKT signalling module in PD brains is crucial because impaired balance between the pro-apoptotic and anti-apoptotic pathways trigger unwanted phenotypes such as microglia activation, neuroinflammation, oxidative stress, and apoptosis. These factors continue challenging the brain homeostasis in initial stages thereby essentially assisting the dopaminergic (DA) neurons towards progressive degeneration in PD. Owing to the limitations of sample availability of PD patients, the current research scenario is focused on cellular models of PD which are an excellent source of large drug screening and easy to maintain. Prior to in vitro study, we have done in silico analysis of two major proteins including, Parkin and DJ-1, which are reportedly involved in neuronal damage. Consequently, we have targeted these proteins with selected biomolecules in order to regulate their altered expression in the cells. Further, to validate our results we have performed in vitro experiment as well, where we used 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD model in SHSY5Y neuroblastoma cell lines to study of signalling mechanism and screening of biomolecules in an attempt to reverse disease symptoms in PD.