Hyperactivation of Hedgehog signaling impedes myelin development and repair via cholesterol dysregulation in oligodendrocytes.

ABSTRACT: The failure to remyelinate demyelinated axons poses a significant challenge in the treatment of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Here, we investigated the role of Hedgehog (Hh) signaling in myelin formation during development and under pathological conditions. Using conditional gain-of-function analyses, we found that hyperactivation of Hh signaling in oligodendrocyte precursor cells (OPCs) inhibits oligodendrocyte (OL) differentiation and myelination. Notably, sustained activation of Hh signaling in adult OPCs hinders myelin repair following LPC-induced focal demyelination. Through RNA sequencing, we discovered that genes associated with cholesterol synthesis were upregulated, and observed intracellular cholesterol accumu

SUBMITTER: Fang M 

PROVIDER: S-EPMC11615242 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature