{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T03:35:10Z","timestamp":1768448110520,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Joint Programme-Neurodegenerative Disease Research","award":["JPND 01ED2005B, GBA-PaCTS"],"award-info":[{"award-number":["JPND 01ED2005B, GBA-PaCTS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neuron-to-neuron transfer of pathogenic \u03b1-synuclein species is a mechanism of likely relevance to Parkinson\u2019s disease development. Experimentally, interneuronal \u03b1-synuclein spreading from the low brainstem toward higher brain regions can be reproduced by the administration of AAV vectors encoding for \u03b1-synuclein into the mouse vagus nerve. The aim of this study was to determine whether \u03b1-synuclein\u2019s spreading ability is shared by other proteins. Given \u03b1-synuclein synaptic localization, experiments involved intravagal injections of AAVs encoding for other synaptic proteins, \u03b2-synuclein, VAMP2, or SNAP25. Administration of AAV-VAMP2 or AAV-SNAP25 caused robust transduction of either of the proteins in the dorsal medulla oblongata but was not followed by interneuronal VAMP2 or SNAP25 transfer and caudo-rostral spreading. In contrast, AAV-mediated \u03b2-synuclein overexpression triggered its spreading to more frontal brain regions. The aggregate formation was investigated as a potential mechanism involved in protein spreading, and consistent with this hypothesis, results showed that overexpression of \u03b2-synuclein, but not VAMP2 or SNAP25, in the dorsal medulla oblongata was associated with pronounced protein aggregation. Data indicate that interneuronal protein transfer is not a mere consequence of increased expression or synaptic localization. It is rather promoted by structural\/functional characteristics of synuclein proteins that likely include their tendency to form aggregate species.<\/jats:p>","DOI":"10.3390\/cells12040569","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T04:48:03Z","timestamp":1676004483000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Interneuronal In Vivo Transfer of Synaptic Proteins"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0241-4712","authenticated-orcid":false,"given":"Michael","family":"Klinkenberg","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Helwig","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Pinto-Costa","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-6912","authenticated-orcid":false,"given":"Angela","family":"Rollar","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Rusconi","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donato A.","family":"Di Monte","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2840-3429","authenticated-orcid":false,"given":"Ayse","family":"Ulusoy","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41593-018-0238-6","article-title":"Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases","volume":"21","author":"Jucker","year":"2018","journal-title":"Nat. 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