Methionine sulfoxide reductase (Msr) dysfunction in human brain disease

• Published in: Free radical research Vol. 53; no. 11-12; pp. 1144 - 1154
• Main Authors: Reiterer, Melissa, Schmidt-Kastner, Rainald, Milton, Sarah L.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.12.2019
• Subjects: Antioxidants - metabolism; Brain Diseases - enzymology; Genetic Variation - genetics; Genome-wide association study; Humans; Methionine Sulfoxide Reductases - genetics; Methionine Sulfoxide Reductases - metabolism; neurodegenerative disorders; Oxidative Stress; reactive oxygen species; Genome-wide association study; neurodegenerative disorders; oxidative stress; reactive oxygen species
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715762.2019.1662899

Extensive research has shown that oxidative stress is strongly associated with aging, senescence and several diseases, including neurodegenerative and psychiatric disorders. Oxidative stress is caused by the overproduction of reactive oxygen species (ROS) that can be counteracted by both enzymatic and nonenzymatic antioxidants. One of these antioxidant mechanisms is the widely studied methionine sulfoxide reductase system (Msr). Methionine is one of the most easily oxidized amino acids and Msr can reverse this oxidation and restore protein function, with MsrA and MsrB reducing different stereoisomers. This article focuses on experimental and genetic research performed on Msr and its link to brain diseases. Studies on several model systems as well as genome-wide association studies are compiled to highlight the role of MSRA in schizophrenia, Alzheimer's disease, and Parkinson's disease. Genetic variation of MSRA may also contribute to the risk of psychosis, personality traits, and metabolic factors.