Imperial College London
Alternate

Professor Steve Gentleman

Faculty of Medicine, Department of Brain Sciences

Professor of Neuropathology
 
 
 
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Contact

 

+44 (0)20 7594 6586s.gentleman Website

 
 
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Location

 

E407Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Woerman:2017:10.1007/s00401-017-1762-2,
author = {Woerman, AL and Kazmi, SA and Patel, S and Freyman, Y and Oehler, A and Aoyagi, A and Mordes, DA and Halliday, GM and Middleton, LT and Gentleman, SM and Olson, SH and Prusiner, SB},
doi = {10.1007/s00401-017-1762-2},
journal = {Acta Neuropathologica},
pages = {49--63},
title = {MSA prions exhibit remarkable stability and resistance to inactivation.},
url = {http://dx.doi.org/10.1007/s00401-017-1762-2},
volume = {135},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 (PrP(Sc)) prions responsible for Creutzfeldt-Jakob disease (CJD), we investigated MSA transmission under conditions known to result in PrP(Sc) 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 PrP(Sc) 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 PrP(Sc) and α-synuclein prions, arguing that clinicians should exercise caution when working with materials that might contain α-synuclein prions to prevent disease.
AU  - Woerman,AL
AU  - Kazmi,SA
AU  - Patel,S
AU  - Freyman,Y
AU  - Oehler,A
AU  - Aoyagi,A
AU  - Mordes,DA
AU  - Halliday,GM
AU  - Middleton,LT
AU  - Gentleman,SM
AU  - Olson,SH
AU  - Prusiner,SB
DO  - 10.1007/s00401-017-1762-2
EP  - 63
PY  - 2017///
SN  - 1432-0533
SP  - 49
TI  - MSA prions exhibit remarkable stability and resistance to inactivation.
T2  - Acta Neuropathologica
UR  - http://dx.doi.org/10.1007/s00401-017-1762-2
UR  - http://hdl.handle.net/10044/1/53269
VL  - 135
ER  -
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