Tau impedes glioma progression by enhancing fatty acid β-oxidation-induced cellular senescence

Tau (MAPT) expression is inversely associated with glioma malignancy and patient survival. However, the molecular mechanisms underlying this correlation are yet to be fully investigated. This study demonstrated that tau suppressed glioma cell proliferation both in vitro and in vivo. Mechanistically, tau promoted fatty acid β-oxidation, leading to DNA damage and glioma cellular senescence. Functional analyses revealed that tau interacted with carnitine palmitoyltransferase 1A (CPT1A), enhancing CPT1 enzymatic activity and thereby accelerating lipid catabolism. These findings establish tau as a regulator of metabolic reprogramming and senescence in glioma via CPT1-dependent β-oxidation and support its potential as a therapeutic target in glioma management