Evidence map›Paper›PMID 40679367›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.

Linlin Zhou, Yuwei Wang, Yu Liu, Feipeng Zhu, Ge Gao, Chengjie Li, Pu Ai, Jingying Xu, Junxin Wang, Long Guo and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Linlin ZhouShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Yuwei WangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Yu LiuShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Feipeng ZhuState Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Ge GaoCenter for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China.
Chengjie LiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Pu AiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Jingying XuSchool of Medicine, Tongji University, 500 Zhennan Road, Shanghai, 200331, China.
Junxin WangCenter for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China.
Long GuoShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Yuting GuanShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Virginia Man-Yee LeeDepartment of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Jianjun ChenSchool of Medicine, Tongji University, 500 Zhennan Road, Shanghai, 200331, China.
Jialin ZhengCenter for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China.
Qihui WuShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.ORCID https://orcid.org/0000-0001-5979-8297

Funding

Cooperative research project of the Chunhui Program of the Ministry of Education HZKY20220076Fundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of China 82 101 486National Natural Science Foundation of China 82 101 568National Natural Science Foundation of China 82 371 426National Natural Science Foundation of China 82 471 448Ningxia Hui Autonomous Region Key Research and Development Project 2022BFH02012Science and Technology Commission of Shanghai Municipality 23ZR1467900Science and Technology Commission of Shanghai Municipality 24ZR1468500Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine sykyqd02301Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine sykyqd02302Shanghai Pujiang Program 21PJ1412100Shanghai Pujiang Program 24PJA024STI2030-Major Projects 2021ZD0203903
6 · The paper itself

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 nucleation site for αSyn aggregation upon exposure to pathogenic fibrils. Furthermore, Rab7 activation successfully restored endo-lysosomal degradation of αSyn fibrils and reduced inclusion formation in mouse models presenting with both Lewy body and Aβ pathologies. These results highlight the dynein-dependent endo-lysosomal pathway as a promising therapeutic target for mitigating αSyn-related pathologies in co-existing Aβ burden, characteristic of many DLB cases.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesDyneinsLewy Body DiseaseLysosomesalpha-SynucleinAnimalsDisease Models, AnimalEndosomesHippocampusHumansLewy BodiesMiceMice, TransgenicNeuronsrab7 GTP-Binding Proteinsalpha-SynucleinAmyloid beta-PeptidesDyneinsrab7 GTP-Binding ProteinsAβdyneinendo‐lysosomal degradationLewy body disorderα‐synuclein

Identifiers

PMID40679367
PMCPMC12499460

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.