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Compelling evidence supports the hypothesis that misfolded \u03b1-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, \u03b1-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a <jats:italic>C. elegans<\/jats:italic> model that mirrors this progression and allows us to monitor \u03b1-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo\/endocytosis, affects \u03b1-syn transfer. Furthermore, we demonstrate that silencing <jats:italic>C. elegans<\/jats:italic> orthologs of PD-related genes also increases the accumulation of \u03b1-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of \u03b1-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.<\/jats:p>","DOI":"10.1038\/s41598-017-07383-6","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T08:18:21Z","timestamp":1501661901000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Novel animal model defines genetic contributions for neuron-to-neuron transfer of \u03b1-synuclein"],"prefix":"10.1038","volume":"7","author":[{"given":"Trevor","family":"Tyson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Senchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason F.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-9605","authenticated-orcid":false,"given":"Jeremy M.","family":"Van Raamsdonk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Brundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"7383_CR1","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.tig.2015.01.004","volume":"31","author":"A Verstraeten","year":"2015","unstructured":"Verstraeten, A., Theuns, J. & Van Broeckhoven, C. 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G3 (Bethesda) 2, 1415\u20131425 (2012).","DOI":"10.1534\/g3.112.003830"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07383-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07383-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07383-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:14:25Z","timestamp":1671783265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07383-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,8]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7383"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07383-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,8]]},"assertion":[{"value":"14 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Brundin has received commercial support as a consultant from Renovo Neural, Inc., Roche, Teva\/Lundbeck, and AbbVie. Additionally, he has received commercial support for grants\/research from Renovo and Teva\/Lundbeck. Dr. Brundin has ownership interests in Acousort AB and Parkcell AB. The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7506"}}