These findings, together with observations that many mutant SOD1 subunits retain significant stability and activity, suggest that motor neuron damage in familial amyotrophic lateral sclerosis is caused by the acquisition of injurious properties by mutant SOD1 subunits.
These data support the hypothesis that the loss of motor neurons in familial amyotrophic lateral sclerosis could be due to a reduction in SOD1 activity, possibly potentiated by inefficient glutamate transport.
These results suggest that SOD activity of human fALS mutant CuZnSODs may vary considerably in vivo, with at least some of them retaining a considerable amount of activity.
A new variant Cu/Zn superoxide dismutase (Val7-->Glu) deduced from lymphocyte mRNA sequences from Japanese patients with familial amyotrophic lateral sclerosis.
Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS).
The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis.
Transgenic mice (line G1H) expressing a human SOD1 containing a mutation of Gly-93 --> Ala (G93A) develop a motor neuron disease similar to familial amyotrophic lateral sclerosis, but transgenic mice (line N1029) expressing a wild-type human SOD1 transgene do not.
We conclude that the motor neuron degeneration observed in non-SOD1familial amyotrophic lateral sclerosis is not due to mutations in the KSP repeat of the NEFH gene.
We conclude that the motor neuron degeneration observed in non-SOD1 familial amyotrophic lateral sclerosis is not due to mutations in the KSP repeat of the NEFH gene.
Dominant mutations of the SOD1 gene encoding Cu,Zn superoxide dismutase have been found in members of certain families with familial amyotrophic lateral sclerosis (ALS).
Although defects in the gene encoding the enzyme cytosolic copper/zinc superoxide dismutase (SOD1) have been reported in 20% of familial amyotrophic lateral sclerosis (ALS) patients, the etiology of the remaining familial cases and the more common sporadic form of the disease remains unknown.