Preprint Review Version 1 This version not peer reviewed

Potential Modes of Intercellular Alpha-Synuclein Transmission

Version 1 : Received: 7 February 2017 / Approved: 7 February 2017 / Online: 7 February 2017 (03:24:21 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2017, 18, 469
DOI: 10.3390/ijms18020469

Abstract

Intracellular aggregates of the alpha-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 alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Subject Areas

alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.