Hyperglycemia promotes SIRT3-mediated deacetylation of SARM1 to exacerbate diabetic peripheral neuropathy in mice

ablation in T2DM mice, whereas SARM1 K641Q does not. Our findings establish that SIRT3-mediated deacetylation of SARM1 at K641 drives axonal degeneration in DPN, and enhancing K641 acetylation mitigates disease progression. This study uncovers a critical posttranslational regulation of SARM1 and suggests that targeting the SIRT3-SARM1 axis may offer therapeutic potential for DPN and related neurodegenerative conditions.