Methionine Sulfoxide Reductase in Neurodegenerative Disease and Locomotor-Associated Dopamine Signaling

Abstract

Reactive oxygen species can cause posttranslational modifications to amino acids, including sulfur-containing methionine. Methionine sulfoxide modifications are reduced by methionine sulfoxide reductase enzymes. The redox balance between reactive oxygen species and the methionine sulfoxide reductase system is disrupted in the aging process. This loss of antioxidant homeostasis can result in disease, and neurons may be particularly susceptible to the impact of methionine sulfoxide in proteins. Here we present evidence for the disruption of cell signaling processes in neuronal protein metabolism, and neurodegeneration in organisms lacking the methionine sulfoxide reductase A gene. In addition, we present data supporting the novel concept of the compromising effect of methionine oxidation on dopaminergic receptor function that is linked to movement regulation. Consequently, it is predicted that enhancing the activity of the methionine sulfoxide reductase system may be beneficial in preventing oxidative stress-related changes in brain function and neurodegenerative diseases.