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Int. J. Mol. Sci. 2017, 18(2), 469;

Potential Modes of Intercellular α-Synuclein Transmission

Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia
Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Macquarie University, Sydney 2109, Australia
Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Received: 19 December 2016 / Revised: 1 February 2017 / Accepted: 6 February 2017 / Published: 22 February 2017
(This article belongs to the Special Issue Neuronal Protein Homeostasis in Health and Disease)
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Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of α-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunneling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which α-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease. View Full-Text
Keywords: α-synuclein; Parkinson’s disease; multiple system atrophy; dementia with Lewy bodies; exosome; tunneling nanotube; gliosis; glymphatic α-synuclein; Parkinson’s disease; multiple system atrophy; dementia with Lewy bodies; exosome; tunneling nanotube; gliosis; glymphatic

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Valdinocci, D.; Radford, R.A.W.; Siow, S.M.; Chung, R.S.; Pountney, D.L. Potential Modes of Intercellular α-Synuclein Transmission. Int. J. Mol. Sci. 2017, 18, 469.

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