title: Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein.
abstract: Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson's disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates is associated with the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are transmitted from cell to cell through a cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein and exocytosis of the co-aggregates. Moreover, we find that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promotes propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Bae
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Cheol Soon
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: 1] Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea [2] Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju 220-710, Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jung
authors.affiliation: Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: He-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: ToolGen, Inc., Biotechnology Incubating Center, Seoul National University, Seoul 305-390, Korea.
authors.forename: Seokjoong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Departments of Pathology and Neurosciences, University of California, San Diego, La Jolla, California 92093-0624, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Genzyme, a Sanofi Company, Framingham, Massachusetts 01701, USA.
authors.forename: Sergio Pablo
authors.initials: SP
authors.lastname: Sardi
authors.affiliation: 1] Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea [2] College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D005089:Exocytosis; D055786:Gene Knockout Techniques; D005962:Glucosylceramidase; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D021381:Protein Transport; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D001617:beta-Glucosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D001617:beta-Glucosidase; C517537:GBA2 protein, human; D005962:Glucosylceramidase