{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou L"],"funding":["Fundamental Research Funds for the Central Universities","Science and Technology Commission of Shanghai Municipality","STI2030-Major Projects","Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine","National Natural Science Foundation of China","Cooperative research project of the Chunhui Program of the Ministry of Education","Shanghai Pujiang Program","Ningxia Hui Autonomous Region Key Research and Development Project"],"pagination":["e14860"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499460"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(37)"],"pubmed_abstract":["Dementia with Lewy bodies (DLB) is a significant cause of dementia. However, the limited availability of animal and cellular models that accurately replicate early DLB pathogenesis hampers the understanding of how Aβ plaques influence α-synuclein (αSyn) pathologies. This study addresses this gap by co-culturing primary neurons with adult hippocampal brain slices from either wild-type or Alzheimer's disease (AD) mice containing abundant Aβ plaques and cytokines. Neurons exposed to AD slices showed impaired dynein-dependent organelle trafficking, reducing endosome-lysosome fusion and causing defective degradation of amyloidogenic αSyn fibrils, thus increasing αSyn inclusions. Notably, an abnormal pre-accumulation of dynein in AD mice suggests that dysfunctional dynein may serve as a nucleati"],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology."],"pmcid":["PMC12499460"],"funding_grant_id":["23ZR1467900","82 371 426","82 101 568","82 471 448","HZKY20220076","2021ZD0203903","2022BFH02012","sykyqd02302","24ZR1468500","sykyqd02301","21PJ1412100","24PJA024","82 101 486"],"pubmed_authors":["Zhou L","Li C","Lee VM","Chen J","Wu Q","Ai P","Zhu F","Gao G","Wang J","Xu J","Liu Y","Zheng J","Guo L","Guan Y","Wang Y"],"additional_accession":[]},"is_claimable":false,"name":"Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.","description":"Dementia with Lewy bodies (DLB) is a significant cause of dementia. However, the limited availability of animal and cellular models that accurately replicate early DLB pathogenesis hampers the understanding of how Aβ plaques influence α-synuclein (αSyn) pathologies. This study addresses this gap by co-culturing primary neurons with adult hippocampal brain slices from either wild-type or Alzheimer's disease (AD) mice containing abundant Aβ plaques and cytokines. Neurons exposed to AD slices showed impaired dynein-dependent organelle trafficking, reducing endosome-lysosome fusion and causing defective degradation of amyloidogenic αSyn fibrils, thus increasing αSyn inclusions. Notably, an abnormal pre-accumulation of dynein in AD mice suggests that dysfunctional dynein may serve as a nucleati","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-07-15T05:52:04.838Z","creation":"2026-06-30T03:16:22.525Z"},"accession":"S-EPMC12499460","cross_references":{"pubmed":["40679367"],"doi":["10.1002/advs.202414860"]}}