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Familial amyotrophic lateral sclerosis

  • T. Siddique
  • D. Nijhawan
  • A. Hentati
Conference paper

Summary

Amyotrophic lateral sclerosis is sporadic in ninety percent of cases and familial (FALS) in ten percent. Both forms of FALS whether transmitted as an autosomal dominant (DFALS) or as an autosomal recessive (RFALS) trait is genetically heterogeneous. The locus for one form of RFALS maps to chromosome 2q33. Fifteen percent of DFALS families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) gene which is coded on chromosome 21. These mutations result in decreased SOD1 activity and shortened half-life of the protein in most instances. Transgenic mice overexpressing mutated SOD1 protein develop an ALS-like disease which suggests that the degeneration of motor neurons in DFALS is caused by the gain of a novel toxic function by mutated SOD1 rather than by the decrease of SOD1 activity. Possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed.

Keywords

Amyotrophic Lateral Sclerosis Motor Neuron Motor Neuron Disease Sporadic Amyotrophic Lateral Sclerosis Familial Amyotrophic Lateral Sclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag/Wien 1997

Authors and Affiliations

  • T. Siddique
    • 1
    • 2
    • 3
  • D. Nijhawan
    • 2
  • A. Hentati
    • 3
  1. 1.Department of NeurologyNorthwestern University Medical SchoolChicagoUSA
  2. 2.Department of Cell and Molecular BiologyNorthwestern University Medical SchoolChicagoUSA
  3. 3.Northwestern Institute of NeuroscienceNorthwestern University Medical SchoolChicagoUSA

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