Send to

Choose Destination
Cold Spring Harb Perspect Med. 2018 Jul 2;8(7). pii: a024588. doi: 10.1101/cshperspect.a024588.

α-Synuclein: Multiple System Atrophy Prions.

Author information

Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94158.
Department of Neurology, University of California, San Francisco, San Francisco, California 94158.
Tanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, University of Toronto, Toronto, Ontario M5T 2S8, Canada.
Daiichi Sankyo Company, Limited, Tokyo, 140-8710, Japan.
Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London W6 8RP, United Kingdom.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158.


Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions (GCIs). Several years of studying synthetic α-synuclein fibrils has provided critical insight into the ability of α-synuclein to template endogenous protein misfolding, giving rise to fibrillar structures capable of propagating from cell to cell. However, more recent studies with MSA-derived α-synuclein aggregates have shown that they have a similar ability to undergo template-directed propagation, like PrP prions. Almost 20 years after α-synuclein was discovered as the primary component of GCIs, α-synuclein aggregates isolated from MSA patient samples were shown to infect cultured mammalian cells and also to transmit neurological disease to transgenic mice. These findings argue that α-synuclein becomes a prion in MSA patients. In this review, we discuss the in vitro and in vivo data supporting the recent classification of MSA as a prion disease.

[Available on 2019-07-02]
Free full text

Supplemental Content

Full text links

Icon for HighWire Icon for eScholarship, California Digital Library, University of California
Loading ...
Support Center