Journal of Advanced Clinical Neurology Research

Abstract

Astrocytes possess a pivotal part in sustenance of redox harmony and assisting neuronal survival amongst the central nervous system (CNS). Their antioxidant machinery, mainly implicating i) Nrf2-ARE (nuclear factor erythroid 2-related factor 2-antioxidant response element) pathway, ii) glutathione (GSH) metabolism, and iii) mitochondrial working, making iv) elimination of reactive oxygen and nitrogen species (ROS and RNS) advocate neuronal resistance to oxidative stress (OS). Efficacious connection amongst neurons and astrocytes aligns metabolic and antioxidative reactions through i) glutamate-, ii) nitric oxide-, and iii) calcium- based signalling. Disturbance of such interaction at the time of i) traumatic brain injury (TBI), ii) ischemia, or iii) neurodegenerative diseases (NDD) results in i) redox dysequilibrium, ii) neuroinflammation, and iii) excito toxicity, which allow propagative ND. Astrocytic Nrf2 activation diminishes oxidative injury and inflammation, whereas its reppression optimises the generatio of a neurotoxic glial phenotype. Present corroboration highlights variable therapeutic approaches targeting astrocytic redox mechanistic modes, like i) small-molecule Nrf2 activators, ii) GSH precursors, iii)) mitochondria-targeted antioxidants (MTAs), iv) RNA- and v) gene-dependent strategies. Such arbitrations i) buttress antioxidant capability of astrocytes, ii) impact reactive cell phenotypes, and ii) embrace neuronal rectification in preclinical models. Despite, even now the botherations are present i) in administration ii) safety, iii) and resolution of neuron-glia redox signalling yields favourable approach for neuroprotective therapies having objective of OS - associated CNS damage and disease propa gation. With the advent of modes of cell demise inclusive of ferroptosis, autophagy(mitophagy), getting insight has become easy regarding targeting its constituents like xc− system (cystine/glutamate antiporter), auto phagy factor ATF4 (activating transcription factor4; replenishment of GSH pool by cysteine precursors, for instance N-acetylcysteine (NAC), escalating antioxidant GSH, agents targeting antioxidant enzymes, for in stance a) HO-1 and b) NQO1 diminishing OS markers, lipid peroxidation, mitochondrial ROS etc , mitoQ etc