Oxidative Stress: a common denominator in the pathogenesis of amyotrophic lateral sclerosis.
OBJECTIVE
Amyotrophic lateral sclerosis, or Lou Gehrig disease, is a progressive neurodegenerative disease of adult onset characterized by a loss of motor neurons in the spinal cord and motor cortex. In the last several years, substantial progress has been made in defining the pathogenesis of motor neuron injury and relationships between disease mechanisms and the selective vulnerability of the motor neuron in both familial and sporadic forms of amyotrophic lateral sclerosis.


RESULTS
Current theories have shifted from a neuron-centered pathology to a focus on the interaction between motor neurons and glia, and their respective contributions to pathways implicated in amyotrophic lateral sclerosis. Although multiple mechanisms clearly can contribute to the pathogenesis of motor neuron injury, recent advances suggest that oxidative stress may play a significant role in the amplification, and possibly the initiation, of disease.


CONCLUSIONS
This article reviews the clinical aspects of amyotrophic lateral sclerosis and potential mechanisms of disease pathogenesis in the context of recent data supporting a major role for oxidative stress throughout the disease course. Evidence suggesting an important role for intercellular signaling is emphasized.
Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Ericka P
EP
Simpson
Albert A
AA
Yen
Stanley H
SH
Appel
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000503:physiopathology*; D000975:Antioxidants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D000975:Antioxidants