Myelin Basic Protein Post-Translational Modifications Orchestrate Astrocyte Regulatory Networks.

ABSTRACT: Multiple sclerosis (MS) pathogenesis involves not only immune-mediated myelin injury but also glial responses. We examined how three charge isomers of myelin basic protein (MBP)-native (C1), phosphorylated (C4), and citrullinated (C8)-modulate rat astrocytes. Cytokines were quantified and grouped (pro/anti-inflammatory, chemotactic, neurotrophic, angiogenic, tissue remodeling), and regulatory markers assessed. C1 strongly upregulated the lipid-sensing receptor LXR, and reduced global DNA methylation; C4 moderately enhanced LXR; C8 failed to activate LXR or alter methylation. Functionally, C1 attenuated IL-1β, IL-6 and GM-CSF while increasing IL-10 and certain chemokines. C4 elicited an intermediate pattern, inducing CX3CL1 (fractalkine), CCL20, VEGF-A and TIMP-1 with minor effects on class

SUBMITTER: Ramsden J 

PROVIDER: S-EPMC12921786 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature