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We show that <jats:italic>SNCA<\/jats:italic> Triplication pMac, but not A53T pMac, have significantly increased intracellular \u03b1S versus controls and release significantly more \u03b1S to the medium. <jats:italic>SNCA<\/jats:italic> Triplication pMac, but not A53T pMac, show significantly reduced phagocytosis capability and this can be phenocopied by adding monomeric \u03b1S to the cell culture medium of control pMac. Fibrillar \u03b1S is taken up by pMac by actin-rearrangement-dependent pathways, and monomeric \u03b1S by actin-independent pathways. Finally, pMac degrade \u03b1S and this can be arrested by blocking lysosomal and proteasomal pathways. Together, these results show that macrophages are capable of clearing \u03b1S, but that high levels of exogenous or endogenous \u03b1S compromise this ability, likely a vicious cycle scenario faced by microglia in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1038\/s41598-017-09362-3","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T14:57:59Z","timestamp":1502809079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Excess \u03b1-synuclein compromises phagocytosis in iPSC-derived macrophages"],"prefix":"10.1038","volume":"7","author":[{"given":"Walther","family":"Haenseler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zambon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyne","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Vowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galbha","family":"Duggal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-651X","authenticated-orcid":false,"given":"Katrina","family":"Gwinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Wray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-6269","authenticated-orcid":false,"given":"Kelvin C.","family":"Luk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Wade-Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-6675","authenticated-orcid":false,"given":"Sally A.","family":"Cowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,21]]},"reference":[{"key":"9362_CR1","doi-asserted-by":"publisher","first-page":"8812","DOI":"10.1074\/jbc.275.12.8812","volume":"275","author":"PJ McLean","year":"2000","unstructured":"McLean, P. 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