Dietary supplementation with S-adenosyl methionine delays the onset of motor neuron pathology in a murine model of amyotrophic lateral sclerosis

Neuromolecular Med. 2010 Mar;12(1):86-97. doi: 10.1007/s12017-009-8089-7. Epub 2009 Sep 16.


The full range of causative factors in Amyotrophic lateral sclerosis (ALS) remains elusive, but oxidative stress is recognized as a contributing factor. Mutations in Cu/Zn superoxide dismutase 1 (SOD-1), associated with familial ALS, promote widespread oxidative damage. Mice-expressing G93A mutant human SOD-1 mice display multiple pathological changes characteristic of ALS and are therefore useful for therapeutic development. Dietary supplementation with S-adenosyl methionine (SAM) has provided multiple neuroprotective effects in mouse models of age-related cognitive pathology. We examined herein whether SAM supplementation could affect the course of motor neuron pathology in mice-expressing mutant human SOD-1. SAM delayed disease onset by 2-3 weeks. SAM also delayed hallmarks of neurodegeneration in these mice and in ALS, including preventing loss of motor neurons, and reducing gliosis, SOD-1 aggregation, protein carbonylation, and induction of antioxidant activity. SAM did not increase survival time. These preliminary findings, using a single concentration of SAM, suggest that SAM supplementation maybe useful as part of a comprehensive therapeutic approach for ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / drug therapy
  • Amyotrophic Lateral Sclerosis* / pathology
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Dietary Supplements*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Motor Activity / physiology
  • Motor Neurons* / drug effects
  • Motor Neurons* / pathology
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Oxidative Stress
  • S-Adenosylmethionine* / administration & dosage
  • S-Adenosylmethionine* / pharmacology
  • S-Adenosylmethionine* / therapeutic use
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1


  • SOD1 protein, human
  • S-Adenosylmethionine
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1