SYK regulates Schwann cell metabolic reprogramming to promote axonal regeneration in immune-mediated neuropathy.

ABSTRACT: Immune-mediated peripheral neuropathies like acute motor axonal neuropathy (AMAN) drive axonal degeneration through unresolved neuroinflammation, where Schwann cell (SC) metabolic reprogramming fails to support regeneration. While Spleen Tyrosine Kinase (SYK) is recognized for orchestrating immune responses and central glial function, its role in SC immunometabolism remains unknown. We identify SYK as a master regulator bridging neuroinflammation and SC metabolic adaptation in AMAN. SYK was compensatorily upregulated in SCs at sciatic nerve lesions following anti-GD1a IgG-mediated autoimmune injury, suggesting its activation is part of the protective response. Experimental SYK deficiency triggered catastrophic metabolic collapse, impairing glycolysis and oxidative phosphorylation via dysre

SUBMITTER: Zhang N 

PROVIDER: S-EPMC12825245 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature