Journal article

Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS

Bradley J Turner, Kevin Talbot

PROGRESS IN NEUROBIOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2008

Abstract

Gain-of-function mutations in the Cu,Zn-superoxide dismutase (SOD1) gene are implicated in progressive motor neuron death and paralysis in one form of inherited amyotrophic lateral sclerosis (ALS). At present, transgenic expression of 12 human SOD1 mutations driven by the endogenous promoter is disease-causative and uniformly lethal in mice and rats, despite tremendous biochemical and biophysical variation between the mutants tested. This contrasts with the subclinical motor neuron disease phenotypes of wild-type SOD1 transgenic and knockout mice. Molecular mechanisms such as glutamate-induced excitotoxicity, axonal transport blockade, mitochondrial dysfunction, neuroinflammation and apoptos..

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