The metabolic hypothesis in amyotrophic lateral sclerosis: insights from mutant Cu/Zn-superoxide dismutase mice

Biomed Pharmacother. 2005 May;59(4):190-6. doi: 10.1016/j.biopha.2005.03.003. Epub 2005 Mar 17.


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective loss of motor neurons and progressive muscle atrophy. A subset of patients harbors point mutations in the gene encoding Cu/Zn-superoxide dismutase (SOD1), which allowed the generation of transgenic mice that express different SOD1 mutations and develop an ALS-like pathology. Recently, we reported in these mice the occurrence of a characteristic defect in energy homeostasis and the beneficial effect on the course of the disease of a high-energy fat-enriched diet. In this review, we discuss the implication of these findings in the light of classical clinical observations concerning metabolic alterations in human ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Cell Death*
  • Energy Metabolism
  • Homeostasis / genetics*
  • Humans
  • Mice
  • Motor Neurons / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*


  • Superoxide Dismutase