title: Redox regulation in amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia.
authors.forename: Sonam
authors.initials: S
authors.lastname: Parakh
authors.forename: Damian M
authors.initials: DM
authors.lastname: Spencer
authors.forename: Mark A
authors.initials: MA
authors.lastname: Halloran
authors.forename: Kai Y
authors.initials: KY
authors.lastname: Soo
authors.forename: Julie D
authors.initials: JD
authors.lastname: Atkin
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001343:Autophagy; D001370:Axonal Transport; D002784:Cholesterol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019704:Protein Disulfide-Isomerases / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D002784:Cholesterol; D019704:Protein Disulfide-Isomerases