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Domain-specific proteome remodeling defines mouse myelin aging

Myelin, once regarded as a static insulating structure, is now recognized as a dynamic component of the nervous system, capable of remodeling in response to experience. Its breakd

GIST

Myelin, once regarded as a static insulating structure, is now recognized as a dynamic component of the nervous system, capable of remodeling in response to experience. Its breakdown is linked to cognitive decline and neurodegenerative diseases, often preceding neuronal dysfunction. While the myelin proteome has been studied, the age- and sex-related changes it undergoes remain poorly understood. In this study, we purified myelin proteins from young, middle-aged, and aged male and female mice. Using mass spectrometry-based proteomics, we identified 4,095 unique proteins in males and 3,931 in females, with roughly 30% showing significant age-related changes in both sexes. We find an age-related increase in compact myelin structural proteins, such as MBP, MOBP, and CLDN11, and a selective vulnerability in non-compact myelin cytoskeletal proteins, such as SEPTIN2, SEPTIN8, and OPALIN. Notably, disease-associated proteins previously characterized in single-cell transcriptomics appear at the protein level in aged myelin. To firmly distinguish between proteins derived from oligodendrocytes and other cell types in vivo, we labeled nascent oligodendrocyte proteins with bio-orthogonal non-canonical amino acid tagging (BONCAT).

Clinical Editorial

bioRxiv (Biomedical Preprints) published a clinical update in Research Highlights on 09 Jul 2026. The item focuses on Domain-specific proteome remodeling defines mouse myelin aging. Review the original article for the full source wording and details.

Original source: https://www.biorxiv.org/content/10.64898/2026.07.05.736479v1?rss=1