{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:19:58Z","timestamp":1790518798418,"version":"4.1.0"},"reference-count":84,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS076054"],"award-info":[{"award-number":["R01 NS076054"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32NSO41234"],"award-info":[{"award-number":["T32NSO41234"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lysosomal dysfunction has been implicated in multiple diseases, including lysosomal storage disorders such as Gaucher's disease, in which loss\u2010of\u2010function mutations in the\n                    <jats:italic>GBA1<\/jats:italic>\n                    gene encoding the lysosomal hydrolase \u03b2\u2010glucocerebrosidase result in lipid substrate accumulation. In Parkinson's disease, \u03b1\u2010synuclein accumulates in Lewy bodies and neurites contributing to neuronal death. Previous clinical and genetic evidence has demonstrated an important link between Parkinson's and Gaucher's disease, as\n                    <jats:italic>GBA1<\/jats:italic>\n                    mutations and variants increase the risk of Parkinson's and Parkinson's patients exhibit decreased \u03b2\u2010glucocerebrosidase activity. Using human midbrain neuron cultures, we have found that loss of \u03b2\u2010glucocerebrosidase activity promotes \u03b1\u2010synuclein accumulation and toxicity, whereas \u03b1\u2010synuclein accumulation further contributes to decreased lysosomal \u03b2\u2010glucocerebrosidase activity by disrupting \u03b2\u2010glucocerebrosidase trafficking to lysosomes. Moreover, \u03b1\u2010synuclein accumulation disrupts trafficking of additional lysosomal hydrolases, further contributing to lysosomal dysfunction and neuronal dyshomeostasis. Importantly, promoting \u03b2\u2010glucocerebrosidase activity reduces \u03b1\u2010synuclein accumulation and rescues lysosomal and neuronal dysfunction, suggesting that \u03b2\u2010glucocerebrosidase may be an important therapeutic target for advancing drug discovery in synucleinopathies including Parkinson's disease. \u00a9 2016 International Parkinson and Movement Disorder Society.\n                  <\/jats:p>","DOI":"10.1002\/mds.26802","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T06:43:10Z","timestamp":1473748990000},"page":"1610-1618","source":"Crossref","is-referenced-by-count":56,"title":["Lysosomal trafficking defects link Parkinson's disease with Gaucher's disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Yvette C.","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Krainc","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-106"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10795"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25421"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828727ba"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23894"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17103-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17939"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.10.023"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.06.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.06.001"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3589"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077209"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096284"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1884"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3043"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.487"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.18.2245"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00504-7"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61522-6"},{"key":"e_1_2_7_29_1","first-page":"39","article-title":"The metabolism of glucocerebrosides. 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