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Acta Neuropathologica
Erschienen in: Acta Neuropathologica 1/2018

28.08.2017 | Original Paper

MSA prions exhibit remarkable stability and resistance to inactivation

verfasst von: Amanda L. Woerman, Sabeen A. Kazmi, Smita Patel, Yevgeniy Freyman, Abby Oehler, Atsushi Aoyagi, Daniel A. Mordes, Glenda M. Halliday, Lefkos T. Middleton, Steve M. Gentleman, Steven H. Olson, Stanley B. Prusiner

Erschienen in: Acta Neuropathologica | Ausgabe 1/2018

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Abstract

In multiple system atrophy (MSA), progressive neurodegeneration results from the protein α-synuclein misfolding into a self-templating prion conformation that spreads throughout the brain. MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83+/−), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples. Noting the similarities between α-synuclein prions and PrP scrapie (PrPSc) prions responsible for Creutzfeldt–Jakob disease (CJD), we investigated MSA transmission under conditions known to result in PrPSc transmission. When peripherally exposed to MSA via the peritoneal cavity, hind leg muscle, and tongue, TgM83+/− mice developed neurological signs accompanied by α-synuclein prions in the brain. Iatrogenic CJD, resulting from PrPSc prion adherence to surgical steel instruments, has been investigated by incubating steel sutures in contaminated brain homogenate before implantation into mouse brain. Mice studied using this model for MSA developed disease, whereas wire incubated in control homogenate had no effect on the animals. Notably, formalin fixation did not inactivate α-synuclein prions. Formalin-fixed MSA patient samples also transmitted disease to TgM83+/− mice, even after incubating in fixative for 244 months. Finally, at least 10% sarkosyl was found to be the concentration necessary to partially inactivate MSA prions. These results demonstrate the robustness of α-synuclein prions to denaturation. Moreover, they establish the parallel characteristics between PrPSc and α-synuclein prions, arguing that clinicians should exercise caution when working with materials that might contain α-synuclein prions to prevent disease.
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Metadaten
Titel
MSA prions exhibit remarkable stability and resistance to inactivation
verfasst von
Amanda L. Woerman
Sabeen A. Kazmi
Smita Patel
Yevgeniy Freyman
Abby Oehler
Atsushi Aoyagi
Daniel A. Mordes
Glenda M. Halliday
Lefkos T. Middleton
Steve M. Gentleman
Steven H. Olson
Stanley B. Prusiner
Publikationsdatum
28.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Acta Neuropathologica / Ausgabe 1/2018
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-017-1762-2

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