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Prion Peptides (prion + peptide)
Selected AbstractsAll or none fibrillogenesis of a prion peptideFEBS JOURNAL, Issue 18 2001Wen-Quan Zou Amyloid proteins and peptides comprise a diverse group of molecules that vary both in size and amino-acid sequence, yet assemble into amyloid fibrils that have a common core structure. Kinetic studies of amyloid fibrillogenesis have revealed that certain amyloid proteins form oligomeric intermediates prior to fibril formation. We have investigated fibril formation with a peptide corresponding to residues 195,213 of the human prion protein. Through a combination of kinetic and equilibrium studies, we have found that the fibrillogenesis of this peptide proceeds as an all-or-none reaction where oligomeric intermediates are not stably populated. This variation in whether oligomeric intermediates are stably populated during fibril formation indicates that amyloid proteins assemble into a common fibrillar structure; however, they do so through different pathways. [source] The Role of Prion Peptide Structure and Aggregation in Toxicity and Membrane BindingJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Dawn L. Rymer Abstract: Prion diseases are neurodegenerative disorders associatedwith a conformational change in the normal cellular isoform of the prionprotein, PrPC, to an abnormal scrapie isoform, PrPSC.Unlike the ,-helical PrPC, the protease-resistant core ofPrPSC is predominantly ,-sheet and possesses a tendency topolymerize into amyloid fibrils. We performed experiments with two synthetichuman prion peptides, PrP(106-126) and PrP(127-147), to determine how peptidestructure affects neurotoxicity and protein-membrane interactions. Peptidesolutions possessing ,-sheet and amyloid structures were neurotoxic toPC12 cells in vitro and bound with measurable affinities to cholesterol-richphospholipid membranes at ambient conditions, but peptide solutions lackingstable ,-sheet structures and amyloid content were nontoxic and possessedless than one tenth of the binding affinities of the amyloid-containingpeptides. Regardless of structure, the peptide binding affinities tocholesterol-depleted membranes were greatly reduced. These results suggestthat the ,-sheet and amyloid structures of the prion peptides give riseto their toxicity and membrane binding affinities and that membrane bindingaffinity, especially in cholesterol-rich environments, may be related totoxicity. Our results may have significance in understanding the role of thefibrillogenic cerebral deposits associated with some of the prion diseases inneurodegeneration and may have implications for other amyloidoses. [source] Complete Freund's adjuvant immunization prolongs survival in experimental prion disease in miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Yuval Tal Abstract We recently reported that immunization of mice with certain self-prion protein peptides induced specific T-cell and B-cell immune responses; importantly, this immunization was associated with a decrease in the number of protease-resistant PrPSc particles recoverable in a transplanted, scrapie-infected syngeneic tumor. The present study was carried out to determine whether immunization with the immunogenic PrP peptides might influence the natural history of experimental scrapie in mice. We immunized C57BL/6 mice with self-prion peptides in complete Freund's adjuvant (CFA) or with CFA alone as a control and then infected the mice with mouse-adapted scrapie by injection either intraperitoneally or intracerebrally. We report here that immunization with CFA, irrespective of whether prion peptides were present in the inoculum, resulted in marked prolongation of survival of the mice, whether the challenge was intracerebral or intraperitoneal. Mice in the immunized and control groups that died contained equivalent amounts of PrPSc. Thus, CFA immunization has a therapeutic effect in experimental scrapie in mice, possibly by reducing the rate of PrPSc accumulation in the brain. © 2002 Wiley-Liss, Inc. [source] | ||||||||||