USP9X-mediated deubiquitination of Raptor contributes to autophagy impairment and memory deficits in P301S mice.

ABSTRACT:

Background

Tauopathies, including Alzheimer's disease, are characterized by the pathological aggregation of tau protein, which is strongly linked to dysregulation of the autophagy-lysosomal degradation pathway. However, therapeutic strategies targeting this pathway remain limited.

Methods

We used both in vitro and in vivo models to investigate the role of Raptor in tau pathology. Knockdown of Raptor was performed to assess its impact on mTORC1 activation, autophagy, and tau accumulation. The relationship between USP9X and Raptor was also examined. Pharmacological inhibition of USP9X with WP1130 was employed to further confirm the involvement of the USP9X-Raptor-mTORC1 axis in tau degradation.

Results

Elevated Raptor levels in the hippocampus of P301S mice led to hyper

SUBMITTER: Zheng S 

PROVIDER: S-EPMC11515493 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature