NMDA Receptors Coordinate Metabolic Reprogramming and Mitophagy in Schwann Cells to Promote Peripheral Nerve Regeneration.

ABSTRACT: Schwann cells (SCs) are indispensable for peripheral nerve regeneration, yet the mechanisms enabling their metabolic adaptation to meet the energetic demands of axonal repair remain elusive. Here, we identify N-methyl-D-aspartate (NMDA) receptors as central regulators of SC metabolic plasticity. In a mouse model of acute motor axonal neuropathy, nerve injury led to a marked decrease in NMDA receptor expression on SC. Functional studies revealed that NMDA receptors mediate calcium influx to drive glycolysis and oxidative phosphorylation via the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin and hypoxia-inducible factor-1α/c-Myc pathways, ensuring adenosine triphosphate production for axonal repair. Simultaneously, NMDA receptors orchestrate ataxia telangiect

SUBMITTER: Shan F 

PROVIDER: S-EPMC12322490 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature