BMAL1 upregulates STX17 levels to promote autophagosome-lysosome fusion in hippocampal neurons to ameliorate Alzheimer's disease.

ABSTRACT: We aim to investigate muscle ARNT-like protein 1 (BMAL1) regulation of syntaxin17 (STX17) in mouse hippocampal neurons, focusing on autophagy and amyloid-β (Aβ) deposition. Autophagosome-lysosome fusion in APP/PS1 hippocampal tissues was observed using transmission electron microscopy, while mRNA levels of LC3II and P62 were measured via reverse-transcription PCR (RT-PCR) after Amyloid precursor protein (APP) overexpression. STX17, linked to autophagy and differentially expressed in Alzheimer's disease (AD) brains, was knocked down or overexpressed to assess its effects. The results showed that reduced STX17 impairs autophagosome-lysosome fusion, leading to abnormal Aβ deposition. Coimmunoprecipitation (Co-IP) and immunofluorescence confirmed STX17 interaction with SNAP29 and VAMP8 to form

SUBMITTER: Zhou X 

PROVIDER: S-EPMC11647228 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature