{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:29:55Z","timestamp":1790692195662,"version":"4.1.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100020643","name":"Medical Research Center","doi-asserted-by":"publisher","award":["NRF-2019R1A5A2026045"],"award-info":[{"award-number":["NRF-2019R1A5A2026045"]}],"id":[{"id":"10.13039\/501100020643","id-type":"DOI","asserted-by":"publisher"}]},{"name":"K-Brain Project","award":["RS-2023-00262332"],"award-info":[{"award-number":["RS-2023-00262332"]}]},{"name":"Basic Science Research Program","award":["RS-2024-00460091"],"award-info":[{"award-number":["RS-2024-00460091"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Government"},{"DOI":"10.13039\/501100004199","name":"Okinawa Institute of Science and Technology Graduate University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004199","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Animal models of the pathology of Parkinson's disease (PD) have provided most of the treatments to date, but the disease is restricted to human patients. In vitro models using human pluripotent stem cell (hPSC)-derived neural organoids have provided improved access to study PD aetiology. This study established a method to generate human striatal\u2013midbrain assembloids (hSMAs) from hPSCs for modelling alpha-synuclein (\u03b1-syn) propagation and recapitulating basal ganglia circuits, including nigrostriatal and striatonigral pathways.<\/jats:p>\n                  <jats:p>Human striatal organoids and midbrain organoids were generated using a stepwise differentiation protocol from hPSCs, and both regionalized neural organoids were assembled to form hSMAs, mimicking some basal ganglia circuits. Both the nigrostriatal and striatonigral pathways were present, and the neurons, such as dopaminergic neurons and GABAergic neurons, were electrophysiologically active in the hSMAs. Development of hSMAs in the presence of increased \u03b1-syn from SNCA overexpression induced nigrostriatal system damage, which is typical of the disease. Using the \u03b1-syn-linker-mKO2 reporter and a bimolecular fluorescence complementation system, we demonstrated that fluorescent \u03b1-syn was retrogradely transported from the striatal area to dopaminergic neurons of the midbrain area and exhibited \u03b1-syn aggregates and Lewy body-like inclusions. Furthermore, phosphorylated and detergent-resistant \u03b1-syn aggregates, similar to the pathological form in human patients, accumulated in the midbrain area of hSMAs. Treatment with a protein aggregation inhibitor (Anle138b) and an autophagy inducer (rapamycin) reduced \u03b1-syn aggregation, indicating the potential of hSMAs for drug testing.<\/jats:p>\n                  <jats:p>This study established hSMAs as a novel platform for modelling PD, demonstrating \u03b1-syn propagation and associated neural pathologies. These assembloids offer significant potential for developing therapeutic strategies and understanding the mechanisms of PD progression.<\/jats:p>","DOI":"10.1093\/brain\/awaf326","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T11:45:03Z","timestamp":1756899903000},"page":"867-883","source":"Crossref","is-referenced-by-count":14,"title":["A human striatal\u2013midbrain assembloid model of alpha-synuclein propagation"],"prefix":"10.1093","volume":"149","author":[{"given":"Hoang-Dai","family":"Tran","sequence":"first","affiliation":[{"name":"Brain Mechanism for Behaviour Unit, Okinawa Institute of Science and Technology Graduate University , Okinawa-ken 904-0495 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Kyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"Center for Convergence Research of Neurological Disorders, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin Yi","family":"Yeo","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research , Singapore 138673 ,","place":["Singapore"]},{"name":"Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 119228 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangyong","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Medical Science, College of Medicine, CHA University , Seongnam 13488 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Junaid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Ajou 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Ajou University Medical Center , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-893X","authenticated-orcid":false,"given":"Hyun Goo","family":"Woo","sequence":"additional","affiliation":[{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"Department of Physiology, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"Ajou Translational Omics Center, Ajou University Medical Center , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte R","family":"Denman","sequence":"additional","affiliation":[{"name":"Brain Mechanism for Behaviour Unit, Okinawa Institute of Science and Technology Graduate University , Okinawa-ken 904-0495 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run-Run","family":"Han","sequence":"additional","affiliation":[{"name":"Brain Mechanism for Behaviour Unit, Okinawa Institute of Science and Technology Graduate University , Okinawa-ken 904-0495 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongju","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haerim","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"Center for Convergence Research of Neurological Disorders, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute , Daegu 41062 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-6233","authenticated-orcid":false,"given":"Ji Young","family":"Mun","sequence":"additional","affiliation":[{"name":"Neural Circuit Research Group, Korea Brain Research Institute , Daegu 41062 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3507-5550","authenticated-orcid":false,"given":"Eun Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University , Suwon 16499 ,","place":["Republic of Korea"]},{"name":"Department of Brain Science, Ajou University School of Medicine , Suwon 16499 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1001-4743","authenticated-orcid":false,"given":"Sang Myun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ajou University School of Medicine , Suwon 16499 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