Dietary Supplementation with S-Adenosyl Methionine Delays the Onset of Motor Neuron Pathology in a Murine Model of Amyotrophic Lateral Sclerosis

作者：Suchy James; Lee Sangmook; Ahmed Ambar; Shea Thomas B^*

来源：NeuroMolecular Medicine, 2010, 12(1): 86-97.

DOI：10.1007/s12017-009-8089-7

• Amyotrophic lateral sclerosis
• Motor neuron
• Neuropathology
• S-Adenosyl methionine
• Nutritional supplement
• Transgenic mouse

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.

• 出版日期2010-3