Potential modes of intercellular α-synuclein transmission

Dario Valdinocci, Rowan A. W. Radford, Sue Maye Siow, Roger S. Chung, Dean L. Pountney

    Research output: Contribution to journalReview articlepeer-review

    79 Citations (Scopus)
    22 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Article number469
    Pages (from-to)1-17
    Number of pages17
    JournalInternational Journal of Molecular Sciences
    Volume18
    Issue number2
    DOIs
    Publication statusPublished - 22 Feb 2017

    Keywords

    • α-synuclein
    • Parkinson’s disease
    • multiple system atrophy
    • dementia with Lewy bodies
    • exosome
    • tunneling nanotube
    • gliosis
    • glymphatic

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