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Nat Commun. 2014 Aug 26;5:4755. doi: 10.1038/ncomms5755.

Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein.

Author information

1
Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
2
Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
3
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.
4
ToolGen, Inc., Biotechnology Incubating Center, Seoul National University, Seoul 305-390, Korea.
5
Departments of Pathology and Neurosciences, University of California, San Diego, La Jolla, California 92093-0624, USA.
6
Genzyme, a Sanofi Company, Framingham, Massachusetts 01701, USA.
7
1] Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea [2] College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Korea.

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.

PMID:
25156829
PMCID:
PMC4452288
DOI:
10.1038/ncomms5755
[Indexed for MEDLINE]
Free PMC Article

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