Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age and Alzheimer’s Disease Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways

Version 1 : Received: 30 April 2024 / Approved: 30 April 2024 / Online: 30 April 2024 (17:07:59 CEST)

How to cite: Lopes, F. B. T. P.; Schlatzer, D.; Li, M.; Yilmaz, S.; Wang, R.; Qi, X.; Ayati, M.; Koyuturk, M.; Chance, M. R. Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age and Alzheimer’s Disease Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways. Preprints 2024, 2024042007. https://doi.org/10.20944/preprints202404.2007.v1 Lopes, F. B. T. P.; Schlatzer, D.; Li, M.; Yilmaz, S.; Wang, R.; Qi, X.; Ayati, M.; Koyuturk, M.; Chance, M. R. Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age and Alzheimer’s Disease Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways. Preprints 2024, 2024042007. https://doi.org/10.20944/preprints202404.2007.v1

Abstract

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with nonspecific chemical oxidation from reactive oxygen species (ROS) whose chemistries are linked to various disease pathologies including neurodegeneration. Emerging evidence shows MSox site occupancy is in some cases under enzymatic regulatory control mediating cellular signaling including phosphorylation and/or calcium signaling, raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age, sex and disease dependent MSox speciation in mouse hippocampus. In addition, we explore chemical stability and statistical variance of oxidized peptide signals to understand needed power for MSox based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of mouse hippocampus. Further, the paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for biological discovery novel target identification, and biomarker analysis in ROS and other oxidation linked diseases.

Keywords

Methionine Oxidation; MSox; ROS; Proteomics; 5XFAD; Alzheimer’s Disease, mass spectrometry

Subject

Biology and Life Sciences, Biophysics

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.