Genetics of amyotrophic lateral sclerosis
Open Access
- 1 September 1996
- journal article
- review article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 5 (Supplement) , 1465-1470
- https://doi.org/10.1093/hmg/5.supplement_1.1465
Abstract
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.Keywords
This publication has 58 references indexed in Scilit:
- A rare homozygous phenotype of superoxide dismutase, SOD 2Hereditas, 2009
- Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injuryNature Genetics, 1996
- An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondriaNeuron, 1995
- Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS)Brain Research, 1995
- Mutant Mice, Cu,Zn Superoxide Dismutase, and Motor Neuron DegenerationScience, 1994
- A New Variant Cu/Zn Superoxide Dismutase (Val7→Glu) Deduced from Lymphocyte mRNA Sequences from Japanese Patients with Familial Amyotrophic Lateral SclerosisBiochemical and Biophysical Research Communications, 1994
- A Novel Mutation in Cu/Zn Superoxide Dismutase Gene in Japanese Familial Amyotrophic Lateral SclerosisBiochemical and Biophysical Research Communications, 1994
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993
- Determination and analysis of the 2 Å structure of copper, zinc superoxide dismutaseJournal of Molecular Biology, 1982
- Interaction of hydrogen peroxide with superoxide dismutase from erythrocytesFEBS Letters, 1972