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Oligodendrocyte precursor cell-specific blocking of low glucose-induced activation of AMPK ensures myelination and remyelination

ABSTRACT: In this study, we screening the main types of cerebral cortex cells for glucose sensing and have find that AMPK is not activated in OPCs. We further discover that aldolase C (ALDOC) is acetylated at K14 in OPCs. Expression of ALDOC-K14R, with the acetylation lysine residues changed to arginine, renders OPCs able to activate AMPK in response to low glucose, and suppresses myelin regeneration in cuprizone, Lysolecithin (LPC) and EAE-induced demyelination model. But, genetic depletion of AMPKα1 and AMPKα2 in OPCs prevents the impact of ALDOC-K14R in remyelination. Furthermore, when OPCs activing AMPK with the TRPV antagonist AMG9810 or the hAMPKγ1D317A mutant, the proliferation and differentiation are both inhibited. Thus, our study reveals that ALDOC acetylation in OPCs plays a key role to prevent AMPK activation to endure its myelin repair function in neuronal disorders.

ORGANISM(S): Rattus Rattus Homo Sapiens

SUBMITTER: Chensong Zhang

PROVIDER: PXD067336 | iProX | Wed Aug 13 00:00:00 BST 2025

REPOSITORIES: iProX

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