title: SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disorder that is characterized by the selective death of motor neurons. While the fundamental cause of the disorder is still unclear, the first identified risk gene, Cu,Zn superoxide dismutase (SOD1), has led to the proposal of several mechanisms that are relevant to its pathogenesis. These include excitotoxicity, oxidative stress, ER stress, mitochondrial dysfunction, axonal transport disruption, prion-like propagation, and non-cell autonomous toxicity of neuroglia. Recent evidence suggests that the toxicity of the misfolded wild-type SOD1 (SOD1(WT)) is involved in the pathogenesis of sporadic cases. Yet to what extent SOD1 contributes to neurotoxicity in ALS cases generally is unknown. This review discusses the toxic mechanisms of mutant SOD1 (SOD1(mut)) and misfolded SOD1(WT) in the context of ALS as well as the potential implication of these mechanisms in SOD1 mutation-negative ALS.
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Homma
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: ichijo@mol.f.u-tokyo.ac.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D006801:Humans; D009154:Mutation; D017510:Protein Folding; D000072105:Superoxide Dismutase-1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis (ALS); Cu,Zn superoxide dismutase (SOD1); Familial amyotrophic lateral sclerosis (FALS); Motor neuron; Neurodegeneration; Sporadic amyotrophic lateral sclerosis (SALS)