NEDD4 promotes reactive astrogliosis by enhancing K63-linked ubiquitination and inhibiting chaperone-mediated autophagy degradation of YAP1.

ABSTRACT: Following spinal cord injury (SCI), the transcriptional regulator yes-associated protein 1 (YAP1) is upregulated and accumulates in the nuclei of astrocytes, where it promotes reactive astrogliosis-a process that critically influences wound healing and neurological function recovery. However, the mechanisms regulating YAP1 in reactive astrocytes after SCI remain largely unclear. This study, we identify the E3 ubiquitin ligase NEDD4 as a critical regulator of astrocyte reactive proliferation. NEDD4 enhances astrogliosis by suppressing YAP1 degradation. Conditional deletion of Nedd4 in astrocytes markedly attenuates reactive astrogliosis in vivo, and results in heightened inflammation, exacerbated neuronal injury, and impaired functional recovery following SCI. Importantly, YAP

SUBMITTER: Ye W 

PROVIDER: S-EPMC12781170 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature