NR AJQX
AU Prusiner,S.B.
TI Molecular biology and genetics of prion diseases
QU Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 1994 Mar 29; 343(1306): 447-63
IA http://www.journals.royalsoc.ac.uk/(pkuksk45ynsqzt45ifpjlf45)/app/home/contribution.asp?referrer=parent&backto=issue,16,16;journal,171,225;linkingpublicationresults,1:102022,1
PT journal article; review; review, academic
AB Scrapie was thought for many years to be caused by a virus. Enriching fractions from Syrian hamster (SHa) brain for scrapie infectivity led to the discovery of the prion protein (PrP). To date, no scrapie-specific nucleic acid has been found. As well as scrapie, prion diseases include bovine spongiform encephalopathy (BSE) of cattle, as well as Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome (GSS) of humans. Transgenic (Tg) mice expressing both SHa and mouse (Mo) PrP genes were used to probe the molecular basis of the species barrier and the mechanism of scrapie prion replication. The prion inoculum was found to dictate which prions are synthesized de novo, even though the cells express both PrP genes. Discovery of mutations in the PrP genes of humans with GSS and familial CJD established that prion diseases are both genetic and infectious. Tg mice expressing MoPrP with the GSS point mutation spontaneously develop neurologic dysfunction, spongiform degeneration and astrocytic gliosis. Inoculation of brain extracts prepared from these Tg(MoPrP-P101L) mice produced neurodegeneration in many of the recipient animals after prolonged incubation times. These and other results suggest that prions are devoid of foreign nucleic acid and are thus different from viruses and viroids. Studies on the structure of PrPsc and PrPc suggest that the difference is conformational. Whether one or more putative alpha-helices in PrPc are converted into beta-sheets during synthesis of PrPsc is unknown. Distinct prion isolates or 'strains' exhibit different patterns of PrPsc accumulation which are independent of incubation times. Whether variations in PrPsc conformation are responsible for prion diversity remains to be established. Prion studies have given new insights into the etiologies of infectious, sporadic and inherited degenerative diseases.
IN (Review!) Viele Jahre lang wurde ein Virus als Ursache für Scrapie vermutet. Bis heute wurde aber keine scrapiespezifische Nukleinsäure gefunden. Stattdessen wurde in infektiösem Material das Prionprotein gefunden. Zu den Prion-Krankheiten gehören auch die schwammförmige Rinderenzephalopathie (BSE), die Creutzfeldt-Jakob-Krankheit (CJD) und das Gerstmann-Sträussler-Scheinker Syndrom. Transgene Mäuse mit einem eigenen und einem Priongen aus einem syrischen Hamster bilden Prione aus dem Hamsterprionprotein, wenn sie mit Hamstergewebe infiziert wurden. Nach einer Infektion mit Mausmaterial werden dagegen nur oder fast nur Mausprione gefunden, obwohl die Zellen beide Prionproteinformen produzieren. Die Prionprotein-Krankheiten sind erblich und lassen sich Mutationen im Priongen zuordnen. Gleichzeitig ist die Krankheit von Kranken auf Gesunde übertragbar, also infektiös. Die Umwandlung normaler in infektiöse Prionproteine scheint in einem Umklappen in eine andere Form mit ß-Faltblättern anstatt Alphahelices zu bestehen.
ZR 218
MH Amino Acid Sequence; Animal; Human; Mice; Mice, Transgenic; Models, Biological; Molecular Biology; Molecular Sequence Data; Nucleic Acids/isolation & purification; PrPsc Proteins; Prion Diseases/*etiology/*genetics; Prions/biosynthesis/genetics/isolation & purification; Scrapie/etiology/genetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Neurology, University of California, San Francisco 94143.
SP englisch
PO England