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Methionine sulfoxide reductase (Msr) dysfunction in human brain disease

Melissa Reiterer1, Rainald Schmidt-Kastner2, Sarah L Milton1

  • 1Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL, USA.

Free Radical Research
|November 29, 2019
PubMed

Insights

Oxidative stress contributes to aging and brain diseases. The methionine sulfoxide reductase system (Msr), particularly MSRA, plays a crucial role in protecting against these conditions, impacting risks for schizophrenia and Alzheimer's 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.
Keywords:
Genome-wide association studyneurodegenerative disordersoxidative stressreactive oxygen species

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