Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target.
The cause(s) of amyotrophic lateral sclerosis (ALS) is not fully understood in the vast majority of cases and the mechanisms involved in motor neuron degeneration are multi-factorial and complex. There is substantial evidence to support the hypothesis that oxidative stress is one mechanism by which motor neuron death occurs. This theory becomes more persuasive with the discovery that mutation of the anti-oxidant enzyme, superoxide dismutase 1 (SOD1), causes disease in a significant minority of cases. However, the precise mechanism(s) by which mutant SOD1 leads to motor neuron degeneration have not been defined with certainty, and trials of anti-oxidant therapies have been disappointing. Here, we review the evidence implicating oxidative stress in ALS pathogenesis, discuss how oxidative stress may affect and be affected by other proposed mechanisms of neurodegeneration, and review the trials of various anti-oxidants as potential therapies for ALS.
Barber
Siân C
SC
Academic Neurology Unit, Section of Neuroscience, E Floor, Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Mead
Richard J
RJ
Shaw
Pamela J
PJ
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D008959:Models, Neurological; D015394:Molecular Structure; D009046:Motor Neurons / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics; D000072105:Superoxide Dismutase-1
D000975:Antioxidants; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1