Human Molecular Genetics, Vol 5, 1465-1470, Copyright © 1996 by Oxford University Press
T Siddique and HX Deng
Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by
degeneration of motor neurons in the brain and spinal cord. Identification
of mutations in the gene for Cu,Zn superoxide dismutase (SOD1) in a subset
of ALS families made it possible to develop a transgenic mouse model of ALS
and to investigate its pathogenesis. These investigations suggest that
mutant SOD1 acts through a toxic gain of function which may involve
generation of free radicals. Conformational change in the mutant SOD1
protein, especially the distortion of the 'rim' of the electrostatic
guidance channel may be central to this toxic gain of function and to the
pathogenesis of ALS.
REVIEWS
Genetics of amyotrophic lateral sclerosis
Department of Neurology, Northwestern University Medical School, Chicago, IL 60611, USA.
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