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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,12,12]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Our work uncovers SUMOylation as a major regulator of \u03b1-synuclein fate and pathological aggregation. SUMOylation promotes \u03b1-synuclein accumulation by counteracting \u03b1-synuclein ubiquitination and inhibiting its degradation. SUMOylation also directly causes aggregation of \u03b1-synuclein in vitro and in cells, and the effects are much more prominent with the \u03b1-synuclein disease mutants. Most importantly, levels of SUMOylated \u03b1-synuclein and components of the SUMOylation machinery increase severalfold in Parkinson\u2019s disease (PD) brains and are present in Lewy bodies. Our data indicate a major role of SUMOylation in the pathological aggregation of \u03b1-synuclein and Lewy body formation. 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