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551291 
Journal Article 
Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target 
Barber, SC; Shaw, PJ 
2010 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
In Press, Accepted Manuscript 
5 
629-641 
WOS:000274503100001 
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by death of motor neurons leading to muscle wasting, paralysis and death, usually within 2-3 years of symptom onset. The causes of ALS are not completely understood, and the neurodegenerative processes involved in disease progression are diverse and complex. There is substantial evidence implicating oxidative stress as a central mechanism by which motor neuron death occurs, including: elevated markers of oxidative damage in ALS patient spinal cord and cerebrospinal fluid; and mutations in the anti-oxidant enzyme superoxide dismutase 1 causing approximately 20 % of familial ALS cases. However, the precise mechanism(s) by which mutant SOD1 leads to motor neuron degeneration have not been defined with certainty, and the ultimate trigger for increased oxidative stress in non-SOD1 cases remains unclear. Although some anti-oxidants have shown potential beneficial effects in animal models, human clinical trials of anti-oxidant therapies have so far been disappointing. Here, the evidence implicating oxidative stress in ALS pathogenesis is reviewed, along with how oxidative damage triggers or exacerbates other neurodegenerative processes, and we review the trials of a variety of anti-oxidants as potential therapies for ALS. 
Amyotrophic lateral sclerosis; Anti-oxidant; Oxidative stress; Reactive oxygen species; Superoxide dismutase