NR AXZS
AU Zou,W.Q.; Yuan,J.; Dong,Z.; Guo,J.P.; McGeeham,J.; Xiao,X.; Wang,J.; Cali,I.; Kneale,G.; McGreer,P.L.; Petersen,R.; Gambetti,P.
TI An Increase in PrP*20 Precedes Prion Accumulation
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC7.3
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB
Prion diseases are characterized by the accumulation in the brain and other organs of proteinase K (PK)-resistant prion protein PrPsc. Although it is known that PrPsc is derived from a PK-sensitive cellular PrP (PrPc) via a transition of alpha-helix into betasheets, the mechanism of the conversion of PrPc into PrPsc is poorly understood. The seeding model proposes that a small amount of PrPsc or PrPsc precursor (PrP*) is present in the normal brain in reversible equilibrium with PrPc. When precursor monomeric PrP* molecules form a highly ordered nucleus, PrPc can be converted to PrPsc polymers. Two key elements are required by the seeding model: 1) the presence of a small amount of endogenous PrPsc or PrP* in the uninfected brain; 2) the formation of PrPsc-derived oligomers. However, the presence of the endogenous PrPsc-like species in normal brains, let alone its propensity to form aggregates and convert PrPc, has remained elusive. We have obtained the first evidence that normal human and animal brains contain a novel PrP species called PrP*20. PrP*20 is detergent-insoluble and PK-resistant. Furthermore, it forms aggregates of size similar to those of PrPsc present in prion diseases. PrP*20 is also present in wild type neuroblastoma cells and it is affected by the presence of pathogenic mutations. In addition, PrP*20 was found to be increased in the absence of PrP27-30 in the brain biopsy from a case that then showed prominent PrP27-30 and classical CJD at autopsy suggesting that an increase in the level of PrP*20 characterizes the early stages of prion diseases. Our findings support the existence of prions in normal human brains that may be involved in the pathogenesis of prion diseases. (Richard Bessen and Witold K. Surewicz provided scrapie-infected brain tissues and recombinant
human PrP. Supported by the CJD Foundation, Steris Co., NIH AG14359 and AG08702, CDCUR8/CCU515004, and the Britton Fund).
AD Wen-Quan Zou, J. Yuan, Z. Dong, J.P. Guo, J. McGeeham, X. Xiao, J. Wang, I. Cali, G. Kneale, P.L. McGreer, R. Petersen, P. Gambetti, Case Western Reserve University, USA
SP englisch
PO Schottland