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 article

5 Citations (Scopus)
2 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

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    Valdinocci, D., Radford, R. A. W., Goulding, M., Hayashi, J., Chung, R. S., & Pountney, D. L. (2018). Extracellular interactions of alpha-synuclein in multiple system atrophy. International Journal of Molecular Sciences, 19(12), 1-20. [4129]. https://doi.org/10.3390/ijms19124129