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Consequently, \u03b1-syn has been targeted for the development of therapeutics for PD. We have developed a novel assay to screen compounds with \u03b1-syn modulating properties by mimicking recent findings from <jats:italic>in vivo<\/jats:italic> animal studies involving intrastriatal administration of pre-formed fibrils in mice, resulting in increased \u03b1-syn pathology accompanying the formation of Lewy-body (LB) type inclusions. We found that <jats:italic>in vitro<\/jats:italic> generated \u03b1-syn pre-formed fibrils induce seeding of \u03b1-syn monomers to produce aggregates in a dose-and time-dependent manner under static conditions <jats:italic>in vitro<\/jats:italic>. These aggregates were toxic towards rat pheochromocytoma cells (PC12). Our novel multifunctional dopamine agonists D-519 and D-520 exhibited significant neuroprotection in this assay, while their parent molecules did not. The neuroprotective properties of our compounds were further evaluated in a <jats:italic>Drosophila<\/jats:italic> model of synucleinopathy. Both of our compounds showed protective properties in fly eyes against the toxicity caused by \u03b1-syn. Thus, our <jats:italic>in vitro<\/jats:italic> results on modulation of aggregation and toxicity of \u03b1-syn by our novel assay were further validated with the <jats:italic>in vivo<\/jats:italic> experiments.<\/jats:p>","DOI":"10.1038\/srep38510","type":"journal-article","created":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T10:31:57Z","timestamp":1480933917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Inhibition of alpha-synuclein aggregation by multifunctional dopamine agonists assessed by a novel in vitro assay and an in vivo Drosophila synucleinopathy model"],"prefix":"10.1038","volume":"6","author":[{"given":"Deepthi","family":"Yedlapudi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gnanada S.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokol V.","family":"Todi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloke K.","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,5]]},"reference":[{"key":"BFsrep38510_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1096\/fj.03-0338rev","volume":"18","author":"A Recchia","year":"2004","unstructured":"Recchia, A. et al. 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