Methionine sulfoxide reductase (Msr) dysfunction in human brain disease

Area of Science:

• Biochemistry
• Neuroscience
• Genetics

Background:

• Oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants, is linked to aging, senescence, and various diseases.
• The methionine sulfoxide reductase (Msr) system, comprising MsrA and MsrB, is a key antioxidant mechanism that repairs oxidized methionine residues in proteins.
• Methionine oxidation can impair protein function, and its reversal by Msr is vital for cellular health.

Purpose of the Study:

• To review experimental and genetic evidence linking the Msr system, specifically MSRA, to brain diseases.
• To highlight the role of MSRA in neurodegenerative conditions like Alzheimer's and Parkinson's diseases, and psychiatric disorders such as schizophrenia.
• To explore the potential contribution of MSRA genetic variations to psychosis, personality traits, and metabolic factors.

Main Methods:

• Compilation of experimental research on Msr function in model systems.
• Analysis of genetic studies, including genome-wide association studies (GWAS).
• Review of literature connecting MSRA genetic variations to disease risk and related traits.

Main Results:

• MSRA is implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and Parkinson's disease.
• Genetic variations in MSRA are associated with an increased risk of psychosis.
• MSRA's role extends to influencing personality traits and metabolic factors.

Conclusions:

• The methionine sulfoxide reductase system, particularly MSRA, is a critical antioxidant defense in the brain.
• Dysregulation or genetic variations in MSRA contribute to the risk and progression of major brain disorders.
• Targeting Msr pathways may offer therapeutic strategies for neurodegenerative and psychiatric conditions.