Prions and Brain Diseases in Animals and Humans (Nato Science Series A:, 295)

Most of the world's experts on prions met for a workshop in Erice in August 1996. The aim of the workshop was to discuss the fundamentals of the science ofprions. It was for­ tunate that so many could be present given the pressure that they were under because of the data presented in March 1996, indicating that Bovine Spongiform Encephalopathy, BSE or Mad Cow Disease, had penetrated the species barrier and was beginning to cause a new dis­ ease in humans--the new variant ofCreutzfeldt-Jakob Disease, nvCJD. This important and urgent subject became an additional major topic at the workshop. This is a book containing most of the talks plus the abstracts of those unable to find time to write up their talks. Almost all papers were written in the spring and summer of 1997 and contain material added after the workshop; thus Bob Will's paper on the new variant of cm contains data up to July 1997 and four contributions arrived in October 1997. In addition to the talks given at our workshop, there was a special joint session with the Planetary Emergencies Workshop where many distinguished scientists, including three Nobel laureates, discussed major issues affecting our planet. Six talks were given by us to this other workshop, five about prions, BSE, and nvCJD, and one on the broader issue of new epi­ demics by Luc Montagnier. Although most of the talks concerned research issues, there were a few special talks. Front Matter....Pages i-xiv Introduction — Guide to the Talks....Pages 1-18 Polymorphic Genotype Matching in Acquired Creutzfeldt-Jakob Disease: An Analysis of Donor/Recipient Case Pairs....Pages 19-24 Human Prion Protein Gene Mutation at Codon 183 Associated with an Atypical Form of Prion Disease....Pages 25-32 Fatal Familial Insomnia: A Human Model of Prion Disease....Pages 33-35 Mechanisms of Phenotypic Heterogeneity in Human Prion Diseases....Pages 37-41 Transgenic Mice with Neuron-Specific Expression of a Hamster Prion Protein Minigene Are Susceptible to Hamster Scrapie Agent....Pages 43-47 The Use of Transgenic Mice in the Investigation of Transmissible Spongiform Encephalopathies....Pages 49-57 Large-Scale Sequencing of Human, Mouse, and Sheep Prion Protein Genes....Pages 59-75 Electron Microscopy in Prion Research: Tubulovesicular Structures Are Not Composed of Prion Protein (PrP) but They May Be Intimately Associated with PrP Amyloid Fibrils....Pages 77-86 Familial Prion Diseases Modeled in Cell Culture....Pages 87-98 Yeast Approach to Protein “Prionization”: SUP35-[PSI] System....Pages 99-109 Prions of Yeast: Genetic Evidence that the Non-Mendelian Elements, [PSI] and [URE3] Are Altered Self-Replicating Forms of Sup35p and Ure2p, Respectively....Pages 111-121 Early Clinical Detection of Brain Diseases in Animals....Pages 123-133 Prion Biology and Diseases — Fatal Conformations of Proteins during a Journey from Heresy to Orthodoxy....Pages 135-139 New Variant Creutzfeldt-Jakob Disease....Pages 141-145 The Molecular Basis of Cellular Dysfunction in Prion Diseases....Pages 147-158 Presenilin Proteins and the Pathogenesis of Early-Onset Familial Alzheimer’s Disease: β-Amyloid Production and Parallels to Prion Diseases....Pages 159-176 Polyene Antibiotics in Experimental Transmissible Subacute Spongiform Encephalopathies....Pages 177-185 Scrapie Pathogenesis in Brain Grafts....Pages 187-195 Structural Properties of Recombinant Human Prion Protein....Pages 197-202 Autonomous Folding and Three-Dimensional Structure of the Carboxy-Terminal Domain of the Mouse Prion Protein, PrP(121–231)....Pages 203-216 Protease-Resistant Prion Protein Formation....Pages 217-224 Biophysical Studies on Structure Structural Transitions and Infectivity of the Prion Protein....Pages 225-243 Amyloidogenesis in Transmissible Spongiform Encephalopathies....Pages 245-252 Neuronal Degeneration and Cell Death in Prion Disease....Pages 253-268 Clinical, Pathological, and Molecular Characterization of Gerstmann-Sträussler-Scheinker Disease in the Indiana Kindred ( PRNP F198S)....Pages 269-278 Studies on the Pathogenesis of Scrapie and the Purification of Scrapie Agent in the Hamster Model....Pages 279-284 PrP Peptides as a Tool to Investigate the Pathogenesis of Prion Protein Amyloidoses....Pages 285-289 Properties of the Prion Proteins in Creutzfeldt Jakob Disease Patients Heterozygous for the E200K Mutation....Pages 291-295 Strain Variation in Scrapie and BSE....Pages 297-298 Transmission Studies of Fatal Familial Insomnia....Pages 299-302 Molecular, Genetic and Transgenetic Studies of Human Prion Disease....Pages 303-304 Molecular Biology of Prion Propagation....Pages 305-306 Ultrastructural and Immunocytochemical Studies on Prion Pathogenesis....Pages 307-308 Overview of the BSE Epidemic....Pages 309-309 Assessing Risks of BSE Transmission to Humans....Pages 311-311 Human Activities Are Causing Selection of Pathogenic Agents....Pages 313-313 Pathogenic Similarity of Slow Infections, Induced by Prions and Virions....Pages 315-315 Protein Folding and Misfolding....Pages 317-317 CJD Risk Factors: Analysis of 104 Patients....Pages 319-319 Concluding Talk: Prions from a Physicist’s Viewpoint — Is the ‘Protein Only’ Hypothesis Correct?....Pages 321-339 Back Matter....Pages 341-357