ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Creutzfeldt-Jakob disease, kuru, and Gerstmann-Sträussler syndrome are transmissible degenerative diseases of the central nervous system caused by novel infectious pathogens designated prions. Scrapie is a neurodegenerative disease of sheep and goats and is also caused by prions. Experimental scrapie has been extensively studied in hamsters and mice. The scrapie prion protein (PrPSc) is the only component of the infectious scrapie prion identified, to date. Scrapie infectivity and PrPSccopartition into membranes, rods, and liposomes raising the possibility that only PrPScmight be required for infection; however, a second component such as a small nucleic acid cannot be eliminated. PrPScis encoded by a single copy cellular gene and not by a hypothetical nucleic acid within purified prion preparations. Normal, uninfected cells express the cellular prion protein (PrPc). Both PrPScand PrPcappear to be translated from the same 2.1-kb mRNA. TheN-terminal amino acid sequences of hamster PrPcand PrPScare identical; both correspond to that predicted by the translated prion protein (PrP) gene sequence. While the chemical difference between PrPcand PrPScremains unknown, the organization of the PrP gene argues that it results from a posttranslational event. Six posttranslational modifications of both PrP isoforms have been identified: (1) cleavage of anN-terminal signal peptide, (2) an intramolecular disulfide bond, (3) anN-linked oligosaccharide attached to Asn 181, (4) a second oligosaccharide attached to Asn 197, (5) cleavage of aC-terminal hydrophobic peptide, and (6) a phosphatidylinositol glycolipid attached to theC-terminus. The mouse PrP gene is on chromosome 2 and is linked to a gene controlling the scrapie incubation time (Prn-i). PrP genes from inbred mice with short and long incubation times differ by two amino acids, a finding consistent with but not proving that PrP modulates susceptibility to scrapie. PrPScstimulation of a posttranslational process which converts PrPcor its precursor into PrPScis one possible mechanism for prion replication. This is consistent with observations showing that human prion diseases are manifest as infectious, sporadic and genetic disorders.

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Unconventional slow infections are progressive transmissible degenerative disorders of the central nervous system. The human diseases belonging to this group are Creutz-feld-Jakob disease, kuru, and Gerstmann-Straussler syndrome. Scrapie, transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, and the recently discovered bovine spongiform encephalopathy are similar diseases found in animals. Unusual characteristics of the unconventional slow infections clearly distinguish these disorders from conventional infections. These include: unusually long incubation periods (from months to years); progressive CNS degeneration with characteristic histopathological lesions; the lack of an immune or inflammatory response; unconventional biological and physical properties of the etiologic agents. There has been considerable controversy concerning the nature of the causative agent. The 3 main hypotheses, virus, virino, and modified host protein, are reviewed relative to their ability to explain the properties of the agent and the unusual characteristics of the disease process.The discovery of an abnormal structure, termed scrapie associated fibrils (SAF) and an abnormally modified 33–37 kDa host-encoded glycoprotein unique to unconventional slow infections opened new areas of intense interest and investigation. SAF are abnormal filamentous structures which copurify with infectivity and possess characteristics of “amyloids.” The major component of SAF is the host-encoded scrapie-specific protease resistant glycoprotein. Considerable data has accumulated on the biochemistry, immunology and molecular biology of this host coded scrapie protein. The relationship of SAF and the scrapie-specific protein to the infectious agent is discussed in the context of each of the “nature of the agent” hypotheses.

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Several lines of investigation identify common features of Creutzfeldt-Jakob disease, Alzheimer disease, and retroviral CNS infections. We discuss salient neuropathological, genetic, transmission, and transformation properties that suggest there may be common pathways in the pathogenesis of dementias. We also briefly present potential retroviral mechanisms that may be implicated in all of these dementias.

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1989

数据来源: OVID