Journal
NEUROBIOLOGY OF DISEASE
Volume 42, Issue 3, Pages 360-367Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2011.01.029
Keywords
Alpha-synuclein; Exosome; Transmission; Lysosomal inhibition; Ammonium chloride; Bafilomycin A1
Categories
Funding
- Brain Research Trust (LA), Parkinson's Disease UK
- Wellcome/MRC Parkinson's Disease Consortium
- University of Sheffield
- University of Dundee
- Wellcome Trust [GR087730]
- Department of Health's NIHR Biomedical Research Centres
- MRC [MC_G1000735] Funding Source: UKRI
- Medical Research Council [MC_G1000735] Funding Source: researchfish
- Parkinson's UK [G-0904, F-1101, J-0901, G-0910] Funding Source: researchfish
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Alpha-synuclein aggregation plays a central role in Parkinson's disease pathology. Direct transmission of alpha-synuclein from pathologically affected to healthy unaffected neurons may be important in the anatomical spread of the disease through the nervous system. We have demonstrated that exosomes released from alpha-synuclein over-expressing SH-SY5Y cells contained alpha-synuclein and these exosomes were capable of efficiently transferring alpha-synuclein protein to normal SH-SY5Y cells. Moreover, the incubation of cells with ammonium chloride or bafilomycin A1 to produce the lysosomal dysfunction recently reported in Parkinson's disease led to an increase in the release of alpha-synuclein in exosomes and a concomitant increase in alpha-synuclein transmission to recipient cells. This study clearly demonstrates the importance of exosomes in both the release of alpha synuclein and its transmission between cells and suggests that factors associated with PD pathology accelerate this process. These mechanisms may play an important role in PD pathology and provide a suitable target for therapeutic intervention. (c) 2011 Elsevier Inc. All rights reserved.
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