SIK2-mediated phosphorylation of GABARAPL2 facilitates autophagosome-lysosome fusion and rescues neurodegeneration in an Alzheimer's disease model.

ABSTRACT:

Background

Defective autophagic flux is implicated in Alzheimer's disease (AD), but the molecular mechanisms underlying this process are not fully understood. Salt-inducible kinase 2 (SIK2) is associated with autophagic function. However, its specific involvement in autophagic flux regulation and AD pathogenesis remains unclear.

Methods

We evaluated hippocampal SIK2 expression and its age-related changes in postmortem AD patients and 5 × FAD mice by bioinformatics analysis, immunofluorescence, qPCR, and Western blotting. To investigate the functional role of SIK2, we employed adeno-associated virus-mediated SIK2 knockdown and overexpression in combination with behavioral tests (Morris water maze), electrophysiological recordings (long-term potentiation, LTP), and ultrastruct

SUBMITTER: Dai X 

PROVIDER: S-EPMC12548284 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature