Infectious agent transmission prion diseases

The abnormal deposits found in the brains of CJD victims consist of an abnormal isoform of PrP. Prion protein is normally found in cells. Detailed structural studies show that normal cellular PrP (PrP ) is a soluble protein whose conformation is rich in a-helices with very little P-sheet. The PrP protein extracted from the brains of CJD victims (i.e., PrP ) is identical in primary amino acid sequence to the normal PrP (PrP ). However, PrP has a much greater content of P-sheet conformation with little a-helical structure. Thus PrP is neurotoxic because of its three-dimensional structure. When the prion protein is predominantly in an a-helical conformation it is nontoxic when the prion protein is predominantly in a P-sheet conformation, it kills neurons. The prion protein is thus made neurotoxic not by its amino acid composition but by its conformation. This concept is both fascinating and terrifying. Prion diseases are transmissible thus prions are infectious agents. However, prions are not like bacteria or viruses, or other infectious microbes—they are simply protein molecules. Prions are not microbes with cell membranes and nucleic acids they are not living things. Indeed, prions are not even infectious molecules, they are infectious molecular shapes. 

Prion diseases resulting in encephalopathy can be transmitted between individuals within species (more rarely between species) [26-28], A conformational variant of the normal cellular protein PrPs (PrPc) (protease-sensitive or cellular) is believed to catalyze [29] or nucleate [30-33] conversion to the pathological form, PrPR (protease-resistant). This highly unusual nongenetic mode of transmission of an infectious agent has been strongly debated [29]. The observation of multiple examples of nucleated catalysis of aberrant polymerization of protein subunits has... 

Prions (small proteinaceous infectious particles) are a unique class of infectious agent causing spongiform encephalopathies such as bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. There is considerable concern about the transmission of these agents from infected animals or patients. Risk of infec-tivity is highest in brain, spinal cord and eye tissues. There are still many unknown factors regarding de-... 

Der Trab ist auch eine Krankheit der Schaafe, und ist ansteckend. Sie schleppen sich lange, verzehren sich nach und nach, und zuletzt miissen sie sterben. These sentences are taken from an article published in 1759 [1] and describe two hallmarks of prion diseases or transmissible spongiform encephalopathies (TSEs, summarized in Table 1) The formation and transmission of an infectious particle and the invariably fatal course of these diseases. More than 200 years later a landmark discovery paved the way to study the pathogenesis of prion diseases at a molecular level. Prusiner and colleagues reported the identification of a protease-resistant protein in brain extracts, which co-purified with the infectious scrapie agent [18]. After the N-terminal amino acid sequence of the proteinase K (PK)-resistant core of the prion protein (PrP 27-30) was published in 1984 [19], two... 

The odd properties of the infectious agents of the transmissible spongiform encephalopathies (TSE or prion diseases) evoked proposals that they might represent a distinct class of infectious agents (often called prions), which are proteinaceous and devoid of nucleic acid (Griffith, 1967 Prusiner, 1982 Bolton and Bendheim, 1988 Prusiner,... 

Although PrP-res is associated with TSE infectivity and has, at the biochemical level at least, some limited self-propagating activity, important questions remain about the PrP-only prion model for the TSE agent. For instance, why has no one been able to demonstrate the model s most basic prediction, that is, that PrP-sen alone can be induced to convert to an infectious agent that causes TSE disease when inoculated into animals Inoculation of a synthetic PrP peptide has induced a TSE-like disease in transgenic mice expressing a familial TSE associated mutant PrP, but the serial transmissibility of this disease remains to be determined (Kaneko et al, 2000). Why are 100,000 PrP-res molecules present per infectious unit Why is PrP-res not always found in infectious tissues (Lasmezas et al, 1997) Why are nucleic acids (Akowitz et al,... 

These transmissible diseases, with insoluble protein as the infectious agent, would seem to have originated as mutations, and within this context they became inherited prion diseases. Creutzfeld-Jakob disease, GSS, and FFI number among those now recognized as inherited prion diseases in humans. 

Prion an agent generally responsible for a group of diseases known as spongiform encephalopathies (SE). Transmissible spongiform encephalopathies (TSE) are infectious prion diseases, rather than those that are inherited. Under appropriate conditions, fa-... 

---