Novel structure and genetics of prions causing neurodegeneration in humans and animals.

نویسنده

  • S B Prusiner
چکیده

Over the last 40 years, an impressive array of data has been accumulated indicating that many features of scrapie, kuru, CreutzfeldMakob disease (CJD) and Gerstmann-Straussler syndrome (GSS) are not typical of infectious diseases. Futhermore, the last two decades have witnessed the collection of numerous experimental results which argue strongly that the scrapie agent is a novel pathogen. To distinguish the scrapie and CJD agents from viroids and viruses, the term ‘prion’ was introduced.’ Although scrapie can be transmitted to animals by inoculation with extracts of diseased tissue, whether infection features in the spread of natural scrapie is unclear.2-g Some investigators proposed that natural scrapie is a genetic disease and that its transmissibility is incidenta12s3 while others have argued vehemently that natural scrapie is an infectious disease.a*’ The tripartite manifestations of prion diseasesinfectious, sporadic and genetic-are illustrated by kuru, CJD and GSS, respective1y.l’ Consistent with some of the observations on natural scrapie noted above, GSS and familial CJD are the only known human diseases which appear to be both inherited and transmissible.11-15 Recent genetic linkage studies provide the best evidence, to date, that GSS is a genetic disorder in which infectious prions are produced.” An alternative hypothesis, for which there is little supporting data, is that prions are ubiquitous infectious pathogens causing CJD sporadically across the earth at a rate of one case per million population and GSS in all individuals carrying a mutation in one allele of their prion protein (PrP) gene.10-12,1618 Our genetic linkage results with GSS raise the possibility that sporadic CJD arises from a somatic mutation.5*1’T17 Over the past 5 years, a large amount of experimental data about the particles causing scrapie has accumulated. Most of the information has been confirmed, and much of it is widely accepted.lg At times, this confirmed body of information has been overshadowed by what appears to be controversy due to the diverse terminology used by different laboratories.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Protease-Sensitive Synthetic Prions

Prions arise when the cellular prion protein (PrP(C)) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc). Frequently, PrP(Sc) is protease-resistant but protease-sensitive (s) prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of rec...

متن کامل

An overview of Neurodegeneration with brain iron accumulation (NBIA) syndromes and the disease status in Iranian population: review article

Neurodegeneration with brain iron accumulation (NBIA) is a rare set of inherited neurodegenerative disorders with abnormal accumulation of iron in basal ganglia. It is a clinically and genetically heterogeneous disorder that is characterized by movement disorders, dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset varies from childhood to adulthood and...

متن کامل

Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans.

There is growing concern that bovine spongiform encephalopathy (BSE) may have passed from cattle to humans. We report here that transgenic (Tg) mice expressing bovine (Bo) prion protein (PrP) serially propagate BSE prions and that there is no species barrier for transmission from cattle to Tg(BoPrP) mice. These same mice were also highly susceptible to a new variant of Creutzfeldt-Jakob disease...

متن کامل

Infectious Protein Particle Prions

Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neuro degeneration in a wide range of mammalian hosts, including humans. The causative agent prions are thought to be composed of a rogue isoform of the endogenous prion protein (PrP).Prion diseases or TSEs are a group of rare but fatal neurological disorders that affect humans and a...

متن کامل

Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

Background: Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP. Methods: The proband (index patient) had polyuria, polyd...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Biologicals : journal of the International Association of Biological Standardization

دوره 18 4  شماره 

صفحات  -

تاریخ انتشار 1990