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The inoculation of \u03b1-syn aggregates derived from synucleinopathy or preformed fibrils (PFF) formed in vitro induces misfolding and deposition of endogenous \u03b1-syn. This is referred to as prion-like transmission, and the mechanism is still unknown. In this study, we label \u03b1-syn PFF with quantum dots and visualize their movement directly in acute slices of brain tissue inoculated with \u03b1-syn PFF seeds. Using this system, we find that the trafficking of \u03b1-syn seeds is dependent on fast axonal transport and the seed spreading is dependent on endocytosis and neuronal activity. We also observe pharmacological effects on \u03b1-syn seed spreading; clinically available drugs including riluzole are effective in reducing the spread of \u03b1-syn seeds and this effect is also observed in vivo. Our quantum-dot-labeled \u03b1-syn seed assay system combined with in vivo transmission experiment reveals an early phase of transmission, in which uptake and spreading of seeds occur depending on neuronal activity, and a later phase, in which seeds induce the propagation of endogenous misfolded \u03b1-syn.<\/jats:p>","DOI":"10.1038\/s42003-022-03590-8","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T13:05:16Z","timestamp":1656507916000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Quantum-dot-labeled synuclein seed assay identifies drugs modulating the experimental prion-like transmission"],"prefix":"10.1038","volume":"5","author":[{"given":"Yukio","family":"Imamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayami","family":"Okuzumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Yoshinaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Hiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-372X","authenticated-orcid":false,"given":"Yoshiaki","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Miyasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4545-5100","authenticated-orcid":false,"given":"Nobuyuki","family":"Nukina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"3590_CR1","first-page":"879","volume":"152","author":"M Baba","year":"1998","unstructured":"Baba, M. et al. 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