NR AXXC
AU Steele,A.; Jackson,W.; Hutter,G.; Aguzzi,A.; King,O.; Raymond,G.; Caughey,B.; Lindquist,S.
TI A Critical Role for Heat Shock Factor 1 in Prion Pathogenesis
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC4.8
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB Multiple lines of evidence point toward a critical role for PrP misfolding in prion diseases, yet little is known about how neuronal damage and death relates to the conformational changes in PrP. Very few studies have examined the role of genes other than PrP that are involved in prion pathogenesis. To that end, we have examined the roles of several pathways in prion disease by using mice deficient in genes involved in diverse cellular processes. One of our most promising studies involves the heat shock factor 1 (Hsf1), a key stress responsive transcription factor. Hsf1 up-regulates a variety of genes in response to stress induced by elevated temperature and other events that alter protein folding homeostasis-both genes that are involved in protein turn-over as well as protein re-folding. Importantly, mice deficient for Hsf1 do not suffer from spontaneous neurodegeneration. Hsf1 deficient mice show a marked enhancement of disease when challenged with RML prions (i.c. or i.p.) in terms of survival, behavioral alterations, and pathology. Surprisingly, the accumulation of proteinase-K resistant PrP is delayed in Hsf1 null mice. We are currently examining the accumulation of oligomeric species in Hsf1 null mice as well as the effects of Hsf1 target genes on prion disease.
AD A. Steele, W. Jackson, O. King, S. Lindquist, Whitehead Institute/MIT, USA; G. Hutter, A. Aguzzi, University Hospital, Zürich, Switzerland; G. Raymond, B. Caughey, Rocky Mountain Labs, NIAID, NIH, USA
SP englisch
PO Schottland