{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li M"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["360"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12583606"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Dysregulated autophagy is a hallmark of Alzheimer's disease (AD), yet the extent of impairment in macroautophagy and chaperone-mediated autophagy (CMA) remains unclear. Here, we show that both pathways are disrupted in AD model mice, preceding β-amyloid accumulation and driving disease progression. However, therapeutic autophagy modulation is severely restricted by the blood-brain barrier (BBB). To overcome this, we developed Microglia-Liposome Fusion Extrusion (MiLi-FE), a method to engineer microglia-derived nanovesicles (AR@ENV) for the codelivery of AR7 (a CMA inducer) and rapamycin (a macroautophagy inducer). Leveraging its microglial membrane origin, AR@ENV effectively crosses the BBB and targets inflammatory sites in the AD brain, where it is internalized by neurons. Once inside, th"],"journal":["Signal transduction and targeted therapy"],"pubmed_title":["Microglia-derived nanovesicles synchronize macroautophagy and chaperone-mediated autophagy for Alzheimer's disease therapy."],"pmcid":["PMC12583606"],"funding_grant_id":["NSFC-STINT 82311530116"],"pubmed_authors":["Liu Y","Li J","Wang B","Yang M","Chen F","Chen S","Guo R","Wang Y","He Q","Li M","Zhang Q","Zhu S"],"additional_accession":[]},"is_claimable":false,"name":"Microglia-derived nanovesicles synchronize macroautophagy and chaperone-mediated autophagy for Alzheimer's disease therapy.","description":"Dysregulated autophagy is a hallmark of Alzheimer's disease (AD), yet the extent of impairment in macroautophagy and chaperone-mediated autophagy (CMA) remains unclear. Here, we show that both pathways are disrupted in AD model mice, preceding β-amyloid accumulation and driving disease progression. However, therapeutic autophagy modulation is severely restricted by the blood-brain barrier (BBB). To overcome this, we developed Microglia-Liposome Fusion Extrusion (MiLi-FE), a method to engineer microglia-derived nanovesicles (AR@ENV) for the codelivery of AR7 (a CMA inducer) and rapamycin (a macroautophagy inducer). Leveraging its microglial membrane origin, AR@ENV effectively crosses the BBB and targets inflammatory sites in the AD brain, where it is internalized by neurons. Once inside, th","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T11:36:49.605Z","creation":"2026-05-16T03:11:57.294Z"},"accession":"S-EPMC12583606","cross_references":{"pubmed":["41184271"],"doi":["10.1038/s41392-025-02453-y"]}}