Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission
By L. Álvarez-Erviti, Y. Seow, A. Schapira, C. Gardiner, I. Sargent, M. Wood, J. Cooper. Neurobiology of Disease, 2011
732 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Neurology
View Paper: https://www.semanticscholar.org/paper/7ec6cefba1f5477486dda07b0989dd6899d65ac2
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Citations in the corpus
- Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, unknown): “…a -synuclein is secreted from cultured cells by exocytotic vesicles (Lee et al , 2005; Jang et al , 2010) or via exosomes, which are endosome-derived vesicles secreted during fusion of multivesicular bodies with the plasma membrane (Emmanouilidou et al , 2010; Alvarez-Erviti et al , 2011).”
- Physiological release of endogenous tau is stimulated by neuronal activity (2013, unknown): “Exosomes were prepared from treated and untreated rat cortical neurons as described [33].”
- Exosomal cell-to-cell transmission of alpha synuclein oligomers (2012, background): “Recently, secretion of αsyn in association with membrane vesicles, identified as exosomes based on their composition and biophysical properties, has been described [23,24].”