Dietary Supplementation with S-Adenosyl Methionine Delays the Onset of Motor Neuron Pathology in a Murine Model of Amyotrophic Lateral Sclerosis
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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.
KeywordsAmyotrophic lateral sclerosis Motor neuron Neuropathology S-Adenosyl methionine Nutritional supplement Transgenic mouse
This study was inspired by and is dedicated to the memory of Suzanne Seidel, mother, teacher, and philosopher, who passed away from ALS. This research was supported by internal funds from UMass Lowell. The continued advice of UMass Lowell Veterinarian Dr. Sonja (“Scout”) Chou is greatly appreciated.
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