In infectious and familial prion disorders, neurodegeneration is often seen without obvious deposits of the scrapie prion protein (PrP(Sc)), the principal cause of neuronal death in prion disorders. In such cases, neurotoxicity must be mediated by alternative pathways of cell death. One such pathway is through a transmembrane form of PrP. We have investigated the relationship between intracellu...

Doppel (Dpl) is a PrP-like protein, coded by a gene named PRND, located near the PRNP (prion proten coding gene) locus. Human Dpl is a 179-amino acid protein showing approximately 25% sequence identity with the carboxyproximal two thirds of the human cellular prion protein (PrPC). A comparison of the structures of Dpl and PrP(C) reveals similarities in the secondary structure and topology. Apar...

The 1997 Nobel Prize was awarded to Stanley B. Prusiner for his discovery of prions and there are now wet lab experimental results available which show the evidence of such kind of molecules. Present studies reveal the role of acidic pH in the conversion of human prion protein to the pathogenic isoform is investigated by means of molecular dynamics simulations, focusing the attention to the eff...

The concept of a prion as an infectious self-propagating protein isoform was initially proposed to explain certain mammalian diseases. It is now clear that yeast also has heritable elements transmitted via protein. Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-β aggregates (amyloids). Recently, there has be...

2266 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 12, December 2004 or inherited disease, or as a result of iatrogenic transmission. Prion diseases generated great public concern after an outbreak of bovine spongiform encephalopathy occurred in many European countries and scientific evidence indicated its transmission to humans. Research in prion diseases is hampered by certain...

Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking diverge...

Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, ce...

Human prion disease is known as new variant Creutzfeldt-Jakob disease (CJD), prion protein is not virus, but a special protein which is infectious (protinactious infectious particles, PRION). Creutzfeldt-Jakob disease is a group of infectious prion protein caused by sporadic, dominantly inherited, transmissible neurodegenerative disease, which is characterized by pathologic spongy degeneration ...

Because a definite diagnosis of prion diseases relies on the detection of the abnormal isoform of prion protein (PrPSc), it has been urgently necessary to establish a non-invasive diagnostic test to detect PrPSc in human prion diseases. To evaluate diagnostic usefulness and reliability of the detection of protease-resistant prion protein in urine, we extensively analyzed proteinase K (PK)-resis...