title: Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS ( approximately 90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical modification to reveal an attribute of spinal cord SOD1 common to both SOD1-linked FALS and SALS, but not present in normal or disease-affected tissues from other neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases and spinal muscular atrophy, a non-ALS motor neuron disease. Biotinylation reveals a 32-kDa, covalently cross-linked SOD1-containing protein species produced not only in FALS caused by SOD1 mutation, but also in SALS. These studies use chemical modification as a novel tool for the detection of a disease-associated biomarker. Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS.
authors.affiliation: Bioconformatics Laboratory and Department of Neuroscience, California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Gruzman
authors.forename: William L
authors.initials: WL
authors.lastname: Wood
authors.forename: Evgenia
authors.initials: E
authors.lastname: Alpert
authors.forename: M Dharma
authors.initials: MD
authors.lastname: Prasad
authors.forename: Robert G
authors.initials: RG
authors.lastname: Miller
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.forename: Ronald
authors.initials: R
authors.lastname: Hamilton
authors.forename: Troy D
authors.initials: TD
authors.lastname: Wood
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: Vishwanath R
authors.initials: VR
authors.lastname: Lingappa
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000151:congenital / Q000201:enzymology* / Q000473:pathology; D000941:Antigens / Q000276:immunology; D001344:Autopsy; D001710:Biotin / Q000737:chemistry; D003704:Dementia / Q000201:enzymology / Q000473:pathology; D004198:Disease Susceptibility; D006801:Humans; D008970:Molecular Weight; D009134:Muscular Atrophy, Spinal / Q000201:enzymology / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D000941:Antigens; C000606290:SOD1 protein, human; D001710:Biotin; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1