Five Questions on Prion Diseases 英文参考文献.docVIP

Pearls FiveQuestionsonPrionDiseases AdrianoAguzzi*,CaihongZhu InstituteofNeuropathology,UniversityHospitalofZu¨rich,Zu¨rich,Switzerland Introduction IntracerebralAdministration The most efficient way of prion transmission is intracerebral (i.c)administration. Thisisnotunexpected,sincethebrainisthe main target of prion toxicity and administration to the brain bypasses all natural barriers to prion neuroinvasion, such as the innate and adaptive immune system, as well as the blood–brain barrier. Prion diseases are characterized by deposition of PrPSc , a misfolded and aggregated isoform of the host-encoded cellular prion protein (PrPC), within the central nervous system (CNS) andotherorgans.Herewereviewthecurrentknowledgeonfive issuesrelevanttopriondiseases:(1)howdoprionsenterthebody, (2) how do prions reach the central nervous system, (3) how do prions damage the CNS, (4) do mammals have an antiprion defense system, and (5) how can the prion problem be resolved for good. Several iatrogenic CJD (iCJD) transmissions occurred via neurosurgeryandduramatergrafts.Thesecaseswereparticularly tragic for all those involved because they were inadvertently causedbymedicalpersonnelandrepresentedanuntowardeffect of the intent to treat other ailments. Some of the first well- documented instances of intracerebral prion transmission to humans occurred in Zu¨rich in the 1970s [4]. Electrodes were usedforstereotacticelectroencephalographic(EEG)recordingsin a CJD patient, and reused after sterilization with ethanol and formaldehydevapors—aprocedurethatreliablyinactivatesviruses andbacteria,butisineffectiveagainstprions.Thisresultedinfatal priontransmissiontotwoyoungpatients.Theinfectivityonthese electrodes was later confirmed by transmission of CJD to a chimpanzee. HowDoPrionsEntertheBody? Mostcasesofhumanpriondiseaseoccurforunknownreasons, and.20mutationsinthepriongene(PRNP)mayleadtoinherited priondisease.Inotherinstances,priondiseasesarecontractedby exposure to prion infectivity. S