articleProceedings of the National Academy of SciencesAug 31, 2015BRONZE OA

Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism

University of California, San Francisco · Institute for Neurodegenerative Disorders · +8 more institutions

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Abstract

Prions are proteins that adopt alternative conformations that become self-propagating; the PrP(Sc) prion causes the rare human disorder Creutzfeldt-Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing…

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