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We tested whether silencing \u03b1-syn gene expression could reduce native non-aggregated \u03b1-syn substrate and thereby disrupt the propagation of pathological \u03b1-syn initiated by seeding with synucleinopathy-affected mouse brain homogenates. Unilateral intracerebral injections of adeno-associated virus serotype-1 encoding microRNA targeting the \u03b1-syn gene reduced the extent and severity of both the \u03b1-syn pathology and motor deficits. Importantly, a moderate 50% reduction in \u03b1-syn was sufficient to prevent the spread of \u03b1-syn pathology to distal brain regions. Our study combines behavioural, immunohistochemical and biochemical data that strongly support \u03b1-syn knockdown gene therapy for synucleinopathies.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab247","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T13:24:39Z","timestamp":1634649879000},"source":"Crossref","is-referenced-by-count":13,"title":["Viral alpha-synuclein knockdown prevents spreading synucleinopathy"],"prefix":"10.1093","volume":"3","author":[{"given":"Sindhu","family":"Menon","sequence":"first","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, Toronto, ON M5T 0S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke H","family":"Kofoed","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadl","family":"Nabbouh","sequence":"additional","affiliation":[{"name":"Tanz 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