{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:52:16Z","timestamp":1790477536450,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AMED","award":["121ek0109429"],"award-info":[{"award-number":["121ek0109429"]}]},{"name":"AMED","award":["22wm0425015"],"award-info":[{"award-number":["22wm0425015"]}]},{"name":"AMED","award":["24dk0207072"],"award-info":[{"award-number":["24dk0207072"]}]},{"name":"AMED","award":["18K07510"],"award-info":[{"award-number":["18K07510"]}]},{"name":"AMED","award":["21K07444"],"award-info":[{"award-number":["21K07444"]}]},{"name":"AMED","award":["24K10628"],"award-info":[{"award-number":["24K10628"]}]},{"name":"JSPS KAKENHI","award":["121ek0109429"],"award-info":[{"award-number":["121ek0109429"]}]},{"name":"JSPS KAKENHI","award":["22wm0425015"],"award-info":[{"award-number":["22wm0425015"]}]},{"name":"JSPS KAKENHI","award":["24dk0207072"],"award-info":[{"award-number":["24dk0207072"]}]},{"name":"JSPS KAKENHI","award":["18K07510"],"award-info":[{"award-number":["18K07510"]}]},{"name":"JSPS KAKENHI","award":["21K07444"],"award-info":[{"award-number":["21K07444"]}]},{"name":"JSPS KAKENHI","award":["24K10628"],"award-info":[{"award-number":["24K10628"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["121ek0109429"],"award-info":[{"award-number":["121ek0109429"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["22wm0425015"],"award-info":[{"award-number":["22wm0425015"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["24dk0207072"],"award-info":[{"award-number":["24dk0207072"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["18K07510"],"award-info":[{"award-number":["18K07510"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["21K07444"],"award-info":[{"award-number":["21K07444"]}]},{"name":"Juntendo University Research Institute for Diseases of Old Age and Environmental and Gender-specific Medicine","award":["24K10628"],"award-info":[{"award-number":["24K10628"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["121ek0109429"],"award-info":[{"award-number":["121ek0109429"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["22wm0425015"],"award-info":[{"award-number":["22wm0425015"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["24dk0207072"],"award-info":[{"award-number":["24dk0207072"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["18K07510"],"award-info":[{"award-number":["18K07510"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["21K07444"],"award-info":[{"award-number":["21K07444"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["24K10628"],"award-info":[{"award-number":["24K10628"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Parkinson\u2019s disease (PD) is characterized by the pathological accumulation of \u03b1-synuclein (\u03b1-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) within neurons. Growing evidence indicates that \u03b1-syn may propagate throughout the nervous system in a manner similar to prion-like transmission. Extracellular vesicles (EVs) may contribute to this pathway. We and others have reported that ATP13A2\/PARK9 deficiency results in decreased EVs while its overexpression leads to increased EV generation. For analyzing EV-mediated \u03b1-syn secretion in neighboring neurons, we planned to alter Atp13a2 levels in vivo. (2) Methods: Three months after inoculating mouse \u03b1-syn fibrils into the striatum of Atp13a2-null and wild-type mice, we stained brain sections with anti-phosphorylated \u03b1-syn antibodies and then quantified LBs\/LNs. We also examined the effect of increased levels of ATP13A2 by injecting lentivirus carrying human ATP13A2. Finally, we used cultured astrocytes and microglia for \u03b1-syn uptake and release, which were mediated by EVs. (3) Results: While LBs\/LNs were formed in the entire brains, no significant difference was observed in LB\/LN formation between Atp13a2-deficient and wild-type mice. Interestingly, the overexpression of ATP13A2 led to decreased LB\/LN formation in the entire brains. Microglia and astrocytes released EVs more than neurons. EVs released from microglia and astrocytes contained more \u03b1-syn PFFs than those from neurons. (4) Conclusions: These results suggest that enhanced EV secretion by increased ATP13A2 levels attenuate the spreading of \u03b1-syn in brains, suggesting a protective role of ATP13A2 in \u03b1-synucleinopathies<\/jats:p>","DOI":"10.3390\/cells14030163","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T03:40:17Z","timestamp":1737517217000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Altered ATP13A2\/PARK9 Levels Influence \u03b1-Synuclein Accumulation in Neurons via Phagocytosis and Secretion in Glial Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-0708","authenticated-orcid":false,"given":"Taiji","family":"Tsunemi","sequence":"first","affiliation":[{"name":"Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Yoroisaka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dou","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-2556","authenticated-orcid":false,"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nm.4269","article-title":"alpha-synuclein toxicity in neurodegeneration: Mechanism and therapeutic strategies","volume":"23","author":"Wong","year":"2017","journal-title":"Nat. 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