{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:23:15Z","timestamp":1789647795646,"version":"4.0.0"},"reference-count":80,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K06813"],"award-info":[{"award-number":["JP21K06813"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K14401"],"award-info":[{"award-number":["JP23K14401"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H04863"],"award-info":[{"award-number":["JP21H04863"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K18205"],"award-info":[{"award-number":["JP23K18205"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["221032"],"award-info":[{"award-number":["221032"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Research Institute of Fukuoka University","award":["JP21K06813"],"award-info":[{"award-number":["JP21K06813"]}]},{"name":"Central Research Institute of Fukuoka University","award":["JP23K14401"],"award-info":[{"award-number":["JP23K14401"]}]},{"name":"Central Research Institute of Fukuoka University","award":["JP21H04863"],"award-info":[{"award-number":["JP21H04863"]}]},{"name":"Central Research Institute of Fukuoka University","award":["JP23K18205"],"award-info":[{"award-number":["JP23K18205"]}]},{"name":"Central Research Institute of Fukuoka University","award":["221032"],"award-info":[{"award-number":["221032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is characterized by widespread distribution of Lewy bodies, which are composed of phosphorylated and aggregated forms of \u03b1-Synuclein (\u03b1-Syn), in the brain. Although the accumulation and propagation of \u03b1-Syn contribute to the development of PD, the involvement of the blood\u2013brain barrier (BBB) in these processes remains unknown. Pericytes, one of the cell types that constitute the BBB, degrade various forms of \u03b1-Syn. However, the detailed mechanisms involved in \u03b1-Syn degradation by pericytes remain poorly understood. Therefore, in this study, we aimed to determine the ability of the BBB-constituting cells, particularly primary cultures of rat pericytes, brain endothelial cells, and astrocytes, to degrade \u03b1-Syn. After \u03b1-Syn uptake by the cells, intracellular \u03b1-Syn decreased only in pericytes. This pericyte-specific \u03b1-Syn decrease was inhibited by an autophagy inhibitor, bafilomycin A1, and a proteasome inhibitor, MG132. siRNA-mediated knockdown of degradation enzymes or familial PD-associated genes, including cathepsin D, DJ-1, and LRRK2, did not affect \u03b1-Syn clearance in pericytes. However, pharmacological inhibitors of Akt, ERK, and p38 MAPK inhibited \u03b1-Syn degradation by pericytes. In conclusion, our results suggest that \u03b1-Syn degradation by pericytes is mediated by an autophagy\u2013lysosome system and a ubiquitin\u2013proteasome system via \u03b1-Syn-activated Akt, ERK, and p38 MAPK signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms26041615","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"1615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["\u03b1-Synuclein Degradation in Brain Pericytes Is Mediated via Akt, ERK, and p38 MAPK Signaling Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0902-464X","authenticated-orcid":false,"given":"Miki","family":"Yokoya","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuko","family":"Takata","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9510-5928","authenticated-orcid":false,"given":"Takuro","family":"Iwao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-5819","authenticated-orcid":false,"given":"Junichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisataka","family":"Aridome","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Yasunaga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-0510","authenticated-orcid":false,"given":"Shinya","family":"Dohgu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","first-page":"879","article-title":"Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson\u2019s disease and dementia with Lewy bodies","volume":"152","author":"Baba","year":"1998","journal-title":"Am. 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