11. Amyotrophic Lateral Sclerosis

  1. Robert Crichton and
  2. Roberta Ward

Published Online: 6 SEP 2013

DOI: 10.1002/9781118553480.ch11

Metal-based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies

Metal-based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies

How to Cite

Crichton, R. and Ward, R. (eds) (2013) Amyotrophic Lateral Sclerosis, in Metal-based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies, John Wiley and Sons Ltd, Chichester, United Kingdom. doi: 10.1002/9781118553480.ch11

Editor Information

  1. Unit of Biochemistry, Université Catholique de Louvain, Belgium

Publication History

  1. Published Online: 6 SEP 2013
  2. Published Print: 25 OCT 2013

ISBN Information

Print ISBN: 9781119977148

Online ISBN: 9781118553480

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Keywords:

  • amyotrophic lateral sclerosis (ALS);
  • astroglia;
  • endoplasmic reticulum (ER);
  • endoplasmic reticulum stress;
  • glial cells;
  • glutamate transporters;
  • mitochondrial damage;
  • superoxide dismutase 1 (SOD1)

Summary

There are many different possibilities that might be involved in amyotrophic lateral sclerosis (ALS). However, it may be that the selective killing of motor neurons results from the convergence of a series of factors, rather from a single factor. In superoxide dismutase 1 (SOD1) familial ALS, the disease is the consequence of acquired toxicity of mutant SOD1 rather than loss of function. The toxic property affects neurons and glia, and in neurons it probably disrupts protein breakdown by the ubiquitin-proteasome system, affects slow anterograde transport, fast retrograde axonal transport, calcium homoeostasis, mitochondrial function and the maintenance of cytoskeletal architecture. While aggregates are clearly present, it is impossible to determine whether they are protective or pathogenic. There is certainly concurrent damage to astrocytes and microglia, and the loss of glutamate transporters in the astroglial cells is the likely cause of excitotoxic stress to the already damaged motor neurons.