Scrapie and Kuru

Hadlow, W. J.

doi:10.1016/s0140-6736(59)92081-1

Cited by 380 publications

(132 citation statements)

References 7 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…Studies of the molecular agent responsible for scrapie revealed that the entity was extremely resistant to UV and ionizing radiation, treatments that normally inactivated nucleic acids. 7,8 These observations lead to the generally accepted ''protein-only'' hypothesis suggesting that the infectious agent causing prion disease is composed for the most part, if not entirely, of endogenous protein. 1,9 There are two major forms of prion protein: the native and noninfectious form (PrP C ), which has mainly an a-helical structure, and the misfolded infectious form (PrP Sc ), which aggregates into an assembly of b-sheets forming amyloid fibrils.…”

Section: Introductionmentioning

confidence: 99%

Differential stability of the bovine prion protein upon urea unfolding

et al. 2009

View full text Add to dashboard Cite

Prion diseases, or transmissible spongiform encephalopathies, are a group of infectious neurological diseases associated with the structural conversion of an endogenous protein (PrP) in the central nervous system. There are two major forms of this protein: the native and noninfectious cellular form, PrP C ; and the misfolded, infectious, and proteinase K-resistant form, PrP Sc . The C-terminal domain of PrP C is mainly a-helical in structure, whereas PrP Sc in known to aggregate into an assembly of b-sheets, forming amyloid fibrils. To identify the regions of PrP C potentially involved in the initial steps of the conversion to the infectious conformation, we have used high-resolution NMR spectroscopy to characterize the stability and structure of bovine recombinant PrP C (residues 121 to 230) during unfolding with the denaturant urea. Analysis of the 800 MHz 1 H NMR spectra reveals region-specific information about the structural changes occurring upon unfolding. Our data suggest that the dissociation of the native b-sheet of PrP C is a primary step in the urea-induced unfolding process, while strong hydrophobic interactions between helices a1 and a3, and between a2 and a3, stabilize these regions even at very high concentrations of urea.

show abstract

Section: Introductionmentioning

confidence: 99%

Differential stability of the bovine prion protein upon urea unfolding

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The term ''slow virus'' had been coined by Bjorn Sigurdsson in 1954 while he was working in Iceland on scrapie and visna of sheep (17). Five years later, William Hadlow had suggested that kuru, a disease of New Guinea highlanders, was similar to scrapie and thus, it, too, was caused by a slow virus (18). Seven more years were to pass before the transmissibility of kuru was established by passaging the disease to chimpanzees inoculated intracerebrally (19).…”

mentioning

confidence: 99%

Molecular characterization of proteolytic cleavage sites of the Pseudomonas syringae effector AvrRpt2

Chisholm

Dahlbeck

Krishnamurthy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

136

138

View full text Add to dashboard Cite

Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP Sc ). The normal, cellular PrP (PrP C ) is converted into PrP Sc through a posttranslational process during which it acquires a high ␤-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrP Sc . Transgenetic studies argue that PrP Sc acts as a template upon which PrP C is refolded into a nascent PrP Sc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrP Sc . While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.

show abstract

“…The mean duration of illness in kuru was approximately 12 months. The cause of kuru was unknown until the neuropathological changes were noted to resemble those of scrapie, a transmissible spongiform encephalopathy of sheep and goats (Hadlow 1959). Kuru was experimentally transmitted to primates in 1966, thereby becoming the first proven transmissible spongiform encephalopathy of humans (Gajdusek et al 1966).…”

Section: Acquired Human Prion Diseases Kurumentioning

confidence: 99%