Extracellular interactions of alpha-synuclein in multiple system atrophy

Dario Valdinocci, Rowan A. W. Radford, Michael Goulding, Junna Hayashi, Roger S. Chung, Dean L. Pountney*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    20 Citations (Scopus)
    14 Downloads (Pure)

    Abstract

    Multiple system atrophy, characterized by atypical Parkinsonism, results from central nervous system (CNS) cell loss and dysfunction linked to aggregates of the normally pre-synaptic α-synuclein protein. Mostly cytoplasmic pathological α-synuclein inclusion bodies occur predominantly in oligodendrocytes in affected brain regions and there is evidence that α-synuclein released by neurons is taken up preferentially by oligodendrocytes. However, extracellular α-synuclein has also been shown to interact with other neural cell types, including astrocytes and microglia, as well as extracellular factors, mediating neuroinflammation, cell-to-cell spread and other aspects of pathogenesis. Here, we review the current evidence for how α-synuclein present in the extracellular milieu may act at the cell surface to drive components of disease progression. A more detailed understanding of the important extracellular interactions of α-synuclein with neuronal and non-neuronal cell types both in the brain and periphery may provide new therapeutic targets to modulate the disease process.

    Original languageEnglish
    Article number4129
    Pages (from-to)1-20
    Number of pages20
    JournalInternational Journal of Molecular Sciences
    Volume19
    Issue number12
    DOIs
    Publication statusPublished - Dec 2018

    Bibliographical note

    Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Chaperone
    • Gliosis
    • Glymphatic
    • Multiple system atrophy
    • Neuroinflammation
    • α-synuclein

    Fingerprint

    Dive into the research topics of 'Extracellular interactions of alpha-synuclein in multiple system atrophy'. Together they form a unique fingerprint.

    Cite this