[ALS and microglia--a player for non-cell-autonomous neuron death].
Dominant mutation in the gene of superoxide dismutase 1 (SOD1) leads to amyotrophic lateral sclerosis (ALS), an adult-onset progressive fatal motor neuron disease. Recent progress in research on ALS has been made by the use of transgenic mouse model of familial ALS, which expresses mutant form of SOD1 and recapitulates the phenotype and pathology of motor neuron disease. There is accumulating evidence indicating non-cell-autonomous motor neuron death in ALS mouse model. Using the mice carrying deletable mutant SOD1 transgene by the action of Cre recombinase, we have demonstrated that diminishing mutant SOD1 toxicity within microglia significantly slowed disease progression of ALS, indicating the active role of microglia in disease progression of ALS. In this paper, we review the recent advance of ALS research focusing on the role of glial cells in ALS and discuss its prospect.
Yamanaka
Koji
K
Yamanaka Research Unit, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Yamashita
Hirofumi
H
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D019426:Integrases; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000502:physiology*; D009046:Motor Neurons; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics / Q000633:toxicity; D000072105:Superoxide Dismutase-1
D016207:Cytokines; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C045073:Cre recombinase; D019426:Integrases