2012 Fiscal Year Final Research Report

Understanding of spontaneous generation of prions in sporadicCreutzfeld-Jakob disease

Research Project

Project/Area Number	23790998
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Neurology
Research Institution	Nagasaki University
Principal Investigator	SANO Kazunori 長崎大学, 大学院・医歯薬学総合研究科, 助教 (50534343)
Project Period (FY)	2010 – 2012
Keywords	神経分子病態学
Research Abstract	Prion diseases are infectious and fatal neurodegenerative disorders characterized by progressive spongiform changes and the accumulation of abnormal prion protein (PrPSc) in the central nervous system. Although prion diseases were thought to be caused by slow-virus infections, no exogenous viral genome has been identified. The infectious agent, now called prion, is thought not to possess its own genome and to be composed uniquely of prion proteins, which are encoded by the host gene. In this study, we found that polyinosine-polycytidylic acid (poly(I:C)), a synthetic analog of dsRNA,-treated mice increased accumulation of PrPScin prion-infected cells, and accelerated the onset of prion disease in wild-type mice. Moreover, PrPScwas increased by overexpression of Toll-like receptor 3 (TLR3), Retinoic acid-inducible gene-I (RIG-I), and Melanoma differentiation-associated protein 5 (MDA5), which recognize dsRNA, in prion-infected cells. Our findings suggest that dsRNA may play a key role in prion infection.