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Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission

Alvarez-Erviti, L; Seow, Y; Schapira, AH; Gardiner, C; Sargent, IL; Wood, MJA; Cooper, JM; (2011) Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiology of Disease , 42 (3) 360 - 367. 10.1016/j.nbd.2011.01.029. Green open access

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Abstract

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.

Type: Article
Title: Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nbd.2011.01.029
Publisher version: http://doi.org/10.1016/j.nbd.2011.01.029
Language: English
Additional information: Copyright © 2011 Elsevier Inc. Open access under CC BY license.
Keywords: Alpha-synuclein, Exosome, Transmission, Lysosomal inhibition, Ammonium chloride, Bafilomycin A1
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1057013
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