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Oxidative Medicine and Cellular Longevity
Volume 2013 (2013), Article ID 408681, 12 pages
http://dx.doi.org/10.1155/2013/408681
Review Article

Redox Regulation in Amyotrophic Lateral Sclerosis

1Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia
2School of Psychological Science, La Trobe University, Vic 3086, Australia
3Florey Department of Neuroscience, University of Melbourne, Parkville, Vic 3010, Australia

Received 17 October 2012; Revised 7 January 2013; Accepted 10 January 2013

Academic Editor: Jeannette Vasquez-Vivar

Copyright © 2013 Sonam Parakh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.