{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:19:05Z","timestamp":1791422345024,"version":"4.3.3"},"reference-count":184,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Fondo de Investigaci\u00f3n Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER","doi-asserted-by":"publisher","award":["PI20\/00728"],"award-info":[{"award-number":["PI20\/00728"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Fondo de Investigaci\u00f3n Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER","doi-asserted-by":"publisher","award":["HR22-00602"],"award-info":[{"award-number":["HR22-00602"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"Fundaci\u00f3n BBVA (NanoERT), Fundaci\u00f3 La Caixa","doi-asserted-by":"publisher","award":["PI20\/00728"],"award-info":[{"award-number":["PI20\/00728"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"Fundaci\u00f3n BBVA (NanoERT), Fundaci\u00f3 La Caixa","doi-asserted-by":"publisher","award":["HR22-00602"],"award-info":[{"award-number":["HR22-00602"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>GBA gene variants were the first genetic risk factor for Parkinson\u2019s disease. GBA encodes the lysosomal enzyme glucocerebrosidase (GBA), which is involved in sphingolipid metabolism. GBA exhibits a complex physiological function that includes not only the degradation of its substrate glucosylceramide but also the metabolism of other sphingolipids and additional lipids such as cholesterol, particularly when glucocerebrosidase activity is deficient. In the context of Parkinson\u2019s disease associated with GBA, the loss of GBA activity has been associated with the accumulation of \u03b1-synuclein species. In recent years, several hypotheses have proposed alternative and complementary pathological mechanisms to explain why lysosomal enzyme mutations lead to \u03b1-synuclein accumulation and become important risk factors in Parkinson\u2019s disease etiology. Classically, loss of GBA activity has been linked to a dysfunctional autophagy\u2013lysosome system and to a subsequent decrease in autophagy-dependent \u03b1-synuclein turnover; however, several other pathological mechanisms underlying GBA-associated parkinsonism have been proposed. This review summarizes and discusses the different hypotheses with a special focus on autophagy-dependent mechanisms, as well as autophagy-independent mechanisms, where the role of other players such as sphingolipids, cholesterol and other GBA-related proteins make important contributions to Parkinson\u2019s disease pathogenesis.<\/jats:p>","DOI":"10.3390\/cells12010191","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T02:51:39Z","timestamp":1672714299000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The Consequences of GBA Deficiency in the Autophagy\u2013Lysosome System in Parkinson\u2019s Disease Associated with GBA"],"prefix":"10.3390","volume":"12","author":[{"given":"Eddie","family":"Pradas","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Vall d\u2019Hebron Research Institute-CIBERNED, 08035 Barcelona, Spain"},{"name":"Protein Engineering and Nanomedicine Group, Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7053-2625","authenticated-orcid":false,"given":"Marta","family":"Martinez-Vicente","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Vall d\u2019Hebron Research Institute-CIBERNED, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1073\/pnas.1619876114","article-title":"Autophagy Wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in Baker\u2019s Yeast Fuel Advances in Biomedical Research","volume":"114","author":"Levine","year":"2017","journal-title":"Proc. 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