Scrapie

The transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells. They include Creutzfeldt-Jakob disease in humans, scrapie in... 

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

Kocisko DA, Priola SA, Raymond GJ, Chesebro B, Lansbury PT Jr, Caughey B. Species specificity in the cell-free conversion of prion protein to protease-resistant forms a model for the scrapie species barrier. Proc Natl Acad USA 1995 92 3923-3927. 

Lansbury PT Jr, Caughey B. The chemistry of scrapie infection implications of the ice 9 metaphor. Chem Biol 1995 2 1-5. 

Harper JD, Lansbury PT Jr. Models of amyloid seeding in Alzheimer s disease and scrapie mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu Rev Biochem 1997 66 385-407. 

Nguyen JT, Inouye H, Baldwin MA, Fletterick RJ, Cohen FE, Prusiner SB, Kirschner DA. X-ray diffraction of scrapie prion rods and PrP peptides. J Mol Biol 1995 252 412 422. 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

Suggested Alternatives for Differential Diagnosis Sheep Scrapie, pregnancy toxemia, hypocalcemia, tetanus, listeriosis, tick pyemia, hypocuprosis, rabies, hydatid disease, and various plant poisons. Cattle Malignant catarrhal fever, listeriosis, pseudorabies, bovine spongiform encephalopathy, rabies, hypomagnesemia, hypocalcemia, acute lead poisoning, and certain plant poisons. 

The prion diseases are a closely related group of neuro-degenerative conditions which affect both humans and animals. They have previously been described as the subacute spongiform encephalopathies, slow virus diseases and transmissible dementias, and include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and the human prion diseases, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and kuru. Prion diseases are... 

Alper, T. et al. Does the agent of scrapie replicate without nucleic acid Nature 214 764-766,1967. 

Prusiner S. B. Novel proteinaceous infectious particles cause scrapie. Science 216 136-144,1982. 

Bruce, M. etal. Transmission of bovine spongiform encephalopathy and scrapie to mice Strain variation and the species barrier. Philos. Trans. R. Soc. Bond. [Biol] 343 405-411, 1994. 

Alzheimer s disease, Parkinson disease, prion diseases (Creutzfeld-Jacob in humans, scrapie in sheep), Huntington disease, dementia with Levy s bodies, sclerosis multiplex and amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and vascular dementia are the most commonly occurring neurodegenerative diseases, with different (and often unknown) pathophysiology, creating serious health care problems and... 

It is still discussed in the literature whether so-called prion rods isolated from infectious brains (for which amyloid-like structure has been shown) correspond to the structure of the infectious form and/or the structure of the neurotoxic form of PrP. It is also under discussion whether filaments observed in diseased brains (so-called scrapie associated fibers) are similar to prion rods (reviewed in Weissmann, 2005). 

Gasset, M., Baldwin, M. A., Fletterick, R.J., and Prusiner, S. B. (1993). Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infec-... 

Seeger, H., Heikenwalder, M., Zeller, N., Kranich, J., Schwarz, P., Gaspert, A., Seifert, B., Miele, G., and Aguzzi, A. (2005). Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310, 324-326. 

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