The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review

Background: Neurodegeneration is a condition in which progressive loss of function and structure of neurons occurs. Several lines of evidence suggest that oxidative stress has a central role in neurodegenerative diseases. Objective: The aim was to survey molecular mechanisms underlying the involvement of oxidative stress in developing different neurodegenerative diseases. Methods: Original and review articles were retrieved through a PubMed and Google scholar search (from 1989 to 2015) using the following key words: “oxidative stress”, “nerve degeneration” and “neurodegenerative diseases”. Results: A comprehensive analysis of the obtained articles confirmed strong involvement of oxidative stress in the pathophysiology of neurodegenerative diseases through a variety of mechanisms including induction of oxidation of nucleic acids, proteins and lipids, formation of advanced glycation end products, mitochondrial dysfunction, glial cell activation, amyloid β deposition and plaque formation, apoptosis, cytokine production and inflammatory responses, and proteasome dysfunction. Conclusion: Regarding the pivotal role of oxidative stress in neurodegeneration, modulation of free radical production or alleviating their harmful effects can be considered as a potential therapeutic strategy for preventing and controlling neurodegenerative diseases. Accordingly; boosting endogenous antioxidant capacity besides providing exogenous sources of antioxidants merits future research in order to discover new therapeutic agents.