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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>SUMO protein can decorate other proteins via a process called SUMOylation that can regulate toxicity of proteins linked to neurodegenerative diseases. The mutant huntingtin (mHTT) protein in Huntington disease (HD) degenerates nerve cells, and SUMOylation of mHTT makes it more soluble and more toxic to the nerve cells. Here, we show that SUMO deletion in a humanized mouse HD model depletes mHTT and prevents brain shrinkage and behavioral abnormalities. SUMO deletion blocked inflammation and enhanced autophagy, a beneficial cellular degradation pathway. Importantly, ginkgolic acid (GA), a widely used plant supplement that can inhibit SUMOylation, activates autophagy and promotes the degradation of mHTT in human HD cells. 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