{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:40:55Z","timestamp":1787067655227,"version":"build-2736575974"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100013316","name":"Strategic Research Program for Brain Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20dm0107071 and 22ym0126095h0001"],"award-info":[{"award-number":["JP20dm0107071 and 22ym0126095h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06644"],"award-info":[{"award-number":["22K06644"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded \u03b1-synuclein (\u03b1Syn) and myelin disruption. However, the mechanism underlying \u03b1Syn accumulation in MSA brains remains unclear. Here, we aimed to identify epsin-2 as a potential regulator of \u03b1Syn propagation in MSA brains.<\/jats:p>\n                  <jats:p>In the MSA mouse model, PLP-h\u03b1Syn mice, and FABP7\/\u03b1Syn hetero-aggregate-injected mice, we initially discovered that fatty acid-binding protein 7 (FABP7) is related to MSA development and forms hetero-aggregates with \u03b1Syn, which exhibit stronger toxicity than \u03b1Syn aggregates. Moreover, the injected FABP7\/\u03b1Syn hetero-aggregates in mice selectively accumulated only in oligodendrocytes and Purkinje neurons, causing cerebellar dysfunction.<\/jats:p>\n                  <jats:p>Furthermore, bioinformatic analyses of whole blood from MSA patients and FABP7 knockdown mice revealed that epsin-2, a protein expressed in both oligodendrocytes and Purkinje cells, could potentially regulate FABP7\/\u03b1Syn hetero-aggregate propagation via clathrin-dependent endocytosis.<\/jats:p>\n                  <jats:p>Lastly, adeno-associated virus type 5-dependent epsin-2 knockdown mice exhibited decreased levels of \u03b1Syn aggregate accumulation in Purkinje neurons and oligodendrocytes, as well as improved myelin levels and Purkinje neuron function in the cerebellum and motor performance. These findings suggest that epsin-2 plays a significant role in \u03b1Syn accumulation in MSA, and we propose epsin-2 as a novel therapeutic target for MSA.<\/jats:p>","DOI":"10.1093\/brain\/awad137","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T05:26:46Z","timestamp":1682054806000},"page":"3172-3180","source":"Crossref","is-referenced-by-count":14,"title":["Epsin2, a novel target for multiple system atrophy therapy via \u03b1-synuclein\/FABP7 propagation"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-203X","authenticated-orcid":false,"given":"An","family":"Cheng","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Southwest University , 400715 Chongqing , China"},{"name":"Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"},{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Kawahata","sequence":"additional","affiliation":[{"name":"Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"},{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Sekimori","sequence":"additional","affiliation":[{"name":"Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University , 980-8578 Miyagi , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering & Decision Analytics, Hong Kong University of Science and Technology , 999077 Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, National 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