ANTIOXIDANT THERAPIES TO OXIDATIVE STRESS RELATED NEUROTROPHINS INVOLVED IN ALZHEIMER’S DISEASE

Amit Chaudhary, Rashmi Tripathi, Yashasvi Jain and Satyavani Guttula*

ABSTRACT

Alzheimer Disease (AD) is the most common form of dementia affecting aging population. The pathogenetic process and clinical manifestation of the dementing disorders includes pathophysiological hallmarks (a) extracellular β-amyloid protein's (Aβ) senile plaques deposition (b) intracellular deposition of the microtubule associated protein tau as neurofibrillary tangles (NFTs). Neurotrophins play a vital role in adult neuron survival, maintenance, regeneration besides being required for the correct development of the nervous system. Two neurotrophic factor candidates involved in the progression of AD are NGF and BDNF. Both are affected early in the disease and is initiates a cascade of events. Studies show that antioxidant therapies is a promising therapeutic strategy which show success in pre-clinical studies. Therefore, this paper mainly focuses on the recent developments of commonly used antioxidant therapies for AD and provides indications for future potential antioxidant therapeutic strategies for neurodegenerative diseases. Here, docking of some antioxidants with neurotrophins (like BDNF and NGF) is done using Glide 6.2v. The glide energy calculated can easily predict the rank poses of the different ligands and binding affinity of ten compounds. Theaflavin, Catechin, Luteolin, Kaemferol, Gallic acid, Myricetin, Eriodictyol, Uric acid, Ascorbic and Isorhamnetin acid are top ten highly ranked compounds that produced the best rank poses with three different proteins (1NT3, 1BND, 1B8M). The docking result reveals that these compounds can reduce the oxidative stress, play an important role in reducing the risk or postponing the clinical onset of progressive-dementia and further may enhance the efficacy of antioxidant based treatment strategy.

Keywords: Alzheimer Disease, ?-amyloid protein's, neurofibrillary tangles, Antioxidant, Neurotrophins BDNF, NGF, Oxidative stress