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{Watts:2013:10.1073/pnas.1318268110,
author = {Watts, JC and Giles, K and Oehler, A and Middleton, L and Dexter, DT and Gentleman, SM and DeArmond, SJ and Prusiner, SB},
doi = {10.1073/pnas.1318268110},
journal = {Proceedings of the National Academy of Sciences},
pages = {19555--19560},
title = {Transmission of multiple system atrophy prions to transgenic mice},
url = {http://dx.doi.org/10.1073/pnas.1318268110},
volume = {110},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson’s disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83+/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.
AU  - Watts,JC
AU  - Giles,K
AU  - Oehler,A
AU  - Middleton,L
AU  - Dexter,DT
AU  - Gentleman,SM
AU  - DeArmond,SJ
AU  - Prusiner,SB
DO  - 10.1073/pnas.1318268110
EP  - 19560
PY  - 2013///
SN  - 1091-6490
SP  - 19555
TI  - Transmission of multiple system atrophy prions to transgenic mice
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.1318268110
VL  - 110
ER  -
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