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However, the underlying mechanisms that regulate the formation of \u03b1-syn tetramers remain elusive. Our study shows that mutations in glucocerebrosidase 1 (\n                    <jats:italic>GBA1<\/jats:italic>\n                    ) and depletion-induced GBA1 deficiency leading to accumulation of glycosphingolipids (GSLs) are sufficient to cause destabilization of \u03b1-syn tetramers and increase the susceptibility of human dopaminergic neurons to cytotoxicity due to exposure to pathologic \u03b1-syn fibrils. Therefore, maintaining GBA1 activity and reducing GSLs are potentially important in reducing misfolding and pathogenic aggregation of \u03b1-syn in Parkinson\u2019s disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1700465115","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T15:43:41Z","timestamp":1515426221000},"page":"798-803","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["GBA1 deficiency negatively affects physiological \u03b1-synuclein tetramers and related multimers"],"prefix":"10.1073","volume":"115","author":[{"given":"Sangjune","family":"Kim","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;"},{"name":"Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 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