SOD1 mutation is associated with accumulation of neurofilaments in amyotrophic lateral sclerosis.
Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are found in 15 to 20% of patients with familial amyotrophic lateral sclerosis (FALS). Increased levels of neurofilament subunits in transgenic mouse models of ALS also suggests a key role for these proteins in the pathogenesis of the disease. We report the coexistence of an Ile113-->Thr substitution in exon 4 of the SOD1 gene and marked neurofilamentous pathology in the same FALS patient. These observations suggest that two mechanisms, SOD1-induced toxicity and neurofilament disruption, are acting together.
Rouleau
G A
GA
Centre for Research in Neuroscience, McGill University, Montreal, Quebec, Canada.
Clark
A W
AW
Rooke
K
K
Pramatarova
A
A
Krizus
A
A
Suchowersky
O
O
Julien
J P
JP
Figlewicz
D
D
D000368:Aged; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000235:genetics*; D017354:Point Mutation; D013482:Superoxide Dismutase / Q000235:genetics*
D016900:Neurofilament Proteins; D013482:Superoxide Dismutase