title: α-Synuclein: Multiple System Atrophy Prions.
abstract: 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.
authors.affiliation: 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.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Woerman
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, University of Toronto, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Watts
authors.affiliation: Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94158.|Daiichi Sankyo Company, Limited, Tokyo, 140-8710, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Aoyagi
authors.affiliation: 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.
authors.forename: Kurt
authors.initials: K
authors.lastname: Giles
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London W6 8RP, United Kingdom.
authors.forename: Lefkos T
authors.initials: LT
authors.lastname: Middleton
authors.affiliation: 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.|Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158.
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019578:Multiple System Atrophy / Q000209:etiology*; D017096:Prion Diseases / Q000150:complications* / Q000635:transmission; D011328:Prions / Q000737:chemistry / Q000502:physiology*; D051844:alpha-Synuclein / Q000502:physiology*
chemical_list: D011328:Prions; D051844:alpha-Synuclein