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Pathogenic Mechanisms in Sporadic Amyotrophic Lateral Sclerosis

Published online by Cambridge University Press:  18 September 2015

Eisen Andrew  and
Krieger Charles
Eisen Andrew*
Affiliation:
Neuromuscular Diseases Unit, The Vancouver General Hospital and the University of British Columbia, Vancouver
Krieger Charles
Affiliation:
Neuromuscular Diseases Unit, The Vancouver General Hospital and the University of British Columbia, Vancouver
*
The Neuromuscular Diseases Unit, The Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia, Canada V5Z IM9
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Abstract:

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In recognition of the 100th anniversary of Charcot’s death we have reviewed possible pathogenic mechanisms in amyotrophic lateral sclerosis (ALS). Advances in the last 5 years in molecular biology and genetics have identified mutations in the cytosolic dismutase (SODI) gene in some patients with familial ALS raising the possibility that oxidative stress may be involved in the pathogenesis. An excitotoxic pathogenesis has been implicated based on elevated plasma and CSF levels of amino acids and altered contents of amino acids in the nervous system of ALS patients and changes in the number of excitatory amino acid receptors. ALS sera containing antibodies to L-type calcium channels and the development of immune mediated lower and upper and lower motor neuron models have revitalized research efforts focusing on an immune basis for ALS. Other pathogenic mechanisms which have been the subject of recent research include elemental toxicity, apoptosis and programmed cell death and possibly a deficiency or abnormality in growth factors. Pathogenic processes for ALS must account for an increasing incidence of ALS, male preponderance, and the selective vulnerability of the corticomotoneuronal system.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 20 , Issue 4 , November 1993 , pp. 286 - 296
Copyright
Copyright © Canadian Neurological Sciences Federation 1993

References

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