title: Truncated wild-type SOD1 and FALS-linked mutant SOD1 cause neural cell death in the chick embryo spinal cord.
abstract: Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and approximately 25% of FALS cases are caused by mutations in superoxide dismutase-1 (SOD1). Mutant (MT) SOD1 kills motor neurons because of the mutant protein's toxicity; however, the basis for toxicity is unknown. We electroporated wild-type (WT), truncated WT or MTSOD1 expression constructs into the chick embryo spinal cord. MTSOD1 and truncated WTSOD1 (as small as 36 amino acid residues in length) aggregated in the cytoplasm of cells and caused cell death. These results suggest that MTSOD1 and truncated WTSOD1 lead to neural cell death because of misfolding, and that SOD1 peptides, possibly as a result of proteolytic digestion of MTSOD, play a role in FALS pathogenesis. Electroporation of the chick embryo spinal cord is a useful system in which to investigate neurodegenerative diseases because it provides efficient delivery of genes into neural cells in situ within a living organism.
authors.affiliation: Department of Neurology/MC2030, The University of Chicago Pritzker School of Medicine, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Ghanashyam D
authors.initials: GD
authors.lastname: Ghadge
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.forename: Anna Liza
authors.initials: AL
authors.lastname: Monti
authors.forename: Vytas
authors.initials: V
authors.lastname: Bindokas
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Stevens
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Roos
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D018274:Electroporation; D015870:Gene Expression; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017510:Protein Folding; D013116:Spinal Cord / Q000196:embryology / Q000473:pathology*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C000606290:SOD1 protein, human; C054562:yellow fluorescent protein, Bacteria; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1