Treating Oxidative Neural Injury: Methionine Sulfoxide Reductase Therapy for Parkinson’s Disease

Parkinson’s disease is a common neurodegenerative disease that is characterized by loss of dopaminergic neurons in the substantia nigra and impaired motor function. The disease is multifactorial but oxidative injury is associated with the pathology and contributes to neuronal injury. Fibrillations of α-synuclein are present in pathological lesions in this disease. Oxidation of the sulfur moieties of methionine residues on α-synuclein can contribute to α-synuclein fibrillation. An anti-oxidant enzyme methionine sulfoxide reductase can reverse the methionine oxidation on α-synuclein and act as a sink scavenging reactive oxygen species. Thus, boosting methionine sulfoxide reductase activity may prevent oxidative injury in dopaminergic neurons that contributes to neurodegeneration and impaired neuronal function in Parkinson’s disease. One promising approach to augmenting methionine sulfoxide reductase activity in neurons is to provide a naturally occurring substrate for methionine sulfoxide reductase A, S-methyl-l-cysteine. Recent work in our lab with this compound supports the promise of this substance in preventing or delaying motor dysfunction in multiple model systems of Parkinson’s disease.