Abstract
Mutation in superoxide dismutase-1 (SOD1) causes the inherited degenerative neurological disease familial amyotrophic lateral sclerosis (ALS), a non-cell-autonomous disease: mutant SOD1 synthesis in motor neurons and microglia drives disease onset and progression, respectively. In this issue of the JCI, Harraz and colleagues demonstrate that SOD1 mutants expressed in human cell lines directly stimulate NADPH oxidase (Nox) by binding to Rac1, resulting in overproduction of damaging ROS (see the related article beginning on page 659). Diminishing ROS by treatment with the microglial Nox inhibitor apocynin or by elimination of Nox extends survival in ALS mice, reviving the proposal that ROS mediate ALS pathogenesis, but with a new twist: it's ROS produced by microglia.
Keywords
SOD1ApocyninMicrogliaNADPH oxidaseAmyotrophic lateral sclerosisSuperoxide dismutaseSuperoxideMutantReactive oxygen speciesCell biologyBiologyOxidative stressImmunologyMedicineBiochemistryDiseaseInflammationGenePathology
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Publication Info
- Year
- 2008
- Type
- article
- Volume
- 118
- Issue
- 2
- Pages
- 474-8
- Citations
- 91
- Access
- Closed
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Cite This
Séverine Boillée,
Don W. Cleveland
(2008).
Revisiting oxidative damage in ALS: microglia, Nox, and mutant SOD1.
Journal of Clinical Investigation
, 118
(2)
, 474-8.
https://doi.org/10.1172/jci34613
Identifiers
- DOI
- 10.1172/jci34613