RuNAway Disease: A two cycle model for transmissible spongiform encephalopathies (TSEs) wherein SINE proliferation drives PrP overproduction.

作者: Toby J Gibson

DOI: 10.1186/GB-2001-2-7-PREPRINT0006

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摘要: Despite decades of research, the agent responsible for transmitting spongiform encephalopathies (TSEs) has not been identified. The Prion hypothesis, which dominates field, supposes that modified host PrP protein, termed PrPSc, acts as transmissible agent. This model fits observation TSE diseases elicit almost no immune reaction. transmission verified, however, it possible to produce pure PrPSc aggregates. One long-standing objection is disease agents show classical genetic behaviours, such reproducible strain variation, while also responding selection novel traits adaptation new hosts. Moreover, evidence steadily accumulating infectious titre decoupled from quantity (or even presence) deposits. Rather awkwardly PrP0/0 knockout mice have found incubate and transmit (despite themselves being refractory disease). In this article, a scheme, RuNAway, proposed whereby uncontrolled proliferation type parasitic gene, small dispersed repeat sequences (SINEs), in somatic cells induces overproduction with pathogenic consequences. RuNAway scheme involves twin tandem positive feedback loops: triggering second loop leads disease. consistent long latency period much shorter visible progression typical TSEs.

参考文章(37)
R. G. Rohwer, The scrapie agent: "a virus by any other name". Current Topics in Microbiology and Immunology. ,vol. 172, pp. 195- 232 ,(1991) , 10.1007/978-3-642-76540-7_13
Lisa Timmons, Andrew Fire, Specific interference by ingested dsRNA Nature. ,vol. 395, pp. 854- 854 ,(1998) , 10.1038/27579
Richard Race, Bruce Chesebro, Scrapie infectivity found in resistant species Nature. ,vol. 392, pp. 770- 770 ,(1998) , 10.1038/33834
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888
Dale Schenk, Robin Barbour, Whitney Dunn, Grace Gordon, Henry Grajeda, Teresa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, Mike Lee, Zhenmei Liao, Ivan Lieberburg, Ruth Motter, Linda Mutter, Ferdie Soriano, George Shopp, Nicki Vasquez, Christopher Vandevert, Shannan Walker, Mark Wogulis, Ted Yednock, Dora Games, Peter Seubert, Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. ,vol. 400, pp. 173- 177 ,(1999) , 10.1038/22124
W.-M. Liu, W.-M. Chu, P. V. Choudary, C. W. Schmid, Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts Nucleic Acids Research. ,vol. 23, pp. 1758- 1765 ,(1995) , 10.1093/NAR/23.10.1758
T. G. MALONE, J. S. SEMANCIK, R. F. MARSH, R. P. HANSON, Evidence for the low molecular weight nature of scrapie agent Nature. ,vol. 278, pp. 575- 576 ,(1979) , 10.1038/278575A0
C. I. Lasmezas, J.-P. Deslys, O. Robain, A. Jaegly, V. Beringue, J.-M. Peyrin, J.-G. Fournier, J.-J. Hauw, J. Rossier, D. Dormont, Transmission of the BSE Agent to Mice in the Absence of Detectable Abnormal Prion Protein Science. ,vol. 275, pp. 402- 405 ,(1997) , 10.1126/SCIENCE.275.5298.402
Tikvah Alper, D.A. Haig, M.C. Clarke, The exceptionally small size of the scrapie agent Biochemical and Biophysical Research Communications. ,vol. 22, pp. 278- 284 ,(1966) , 10.1016/0006-291X(66)90478-5