title: Perspective on SOD1 mediated toxicity in Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of spinal motor neurons. Although mutations in dozens of proteins have been associated with ALS, the enzyme, superoxide dismutase 1 (SOD1) was the first protein identified with the development of ALS and accounts for ~20% of familial cases. In experimental animals and patient samples, mutant SOD1 is found in cytoplasmic deposits implicating SOD1 aggregates as the toxic entities. Here we discuss the various biochemical and structure-based hypotheses proposed for mutant SOD1-associated ALS. Although much remains to be discovered about the molecular mechanism of SOD1 mediated toxicity, these hypotheses offer new avenues for therapeutic development.
authors.affiliation: Molecular Biology Institute and Howard Hughes Medical Institute, UCLA, Los Angeles CA, USA.
authors.forename: Smriti
authors.initials: S
authors.lastname: Sangwan
authors.affiliation: Molecular Biology Institute and Howard Hughes Medical Institute, UCLA, Los Angeles CA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Eisenberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D000072105:Superoxide Dismutase-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; superoxide dismutase