The Prion Diseases

Abstract

The prion diseases constitute an unusual group of neurodegenerative disorders. Although they are similar in many ways to other more common diseases, such as Alzheimer disease and amyotrophic lateral sclerosis, they are set apart on the basis of their transmissible nature. In addition to the unique feature of transmissibility, the prion diseases demonstrate that the expression of diverse disease phenotypes is possible from a common etiologic factor. This review provides the reader with a basic understanding of the nature of prions and highlights the clinical and pathologic features of these fascinating diseases.

Presenile dementia syndromes: an update on taxonomy and diagnosis

“…In contrast if codon 129 is valine (and not methionine), the D178N mutation results in a clinical picture typical of Creutzfeldt-Jakob disease rather than fatal familial insomnia. Gerstmann-Sträussler-Scheinker syndrome is associated both with amino acid substitutions at codons 102,105,117,145,198, and 217 and with insertional mutations as well in Prnp. 143 Classically, all prion diseases have a triad of neuropathological features that include vacuolar (spongiform) change, astrogliosis, and neuronal loss.…”

The AGAAAAGA Palindrome in PrP Is Required to Generate a Productive PrPSc-PrPC Complex That Leads to Prion Propagation

“…Once PrP Sc is introduced or spontaneously generated in the brain, it can replicate by complexing with, and templating its conformation onto, additional PrP C (2,3). PrP Sc is distinguished from PrP C in that it is insoluble in non-ionic detergents, displays a relative resistance to proteinase K (PK), 1 and carries a significantly higher content of ␤-sheet structure (4). The molecular mechanisms underlying the conversion and replication of PrP Sc are unknown.…”

“…The prion diseases, the best known of which include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cows, result from the generation and propagation of a conformational variant (PrP Sc ) of the normal prion protein (PrP C ), a predominantly brain-derived glycoprotein of unknown function (1). Once PrP Sc is introduced or spontaneously generated in the brain, it can replicate by complexing with, and templating its conformation onto, additional PrP C (2,3).…”

Live Cell Fluorescence Resonance Energy Transfer Predicts an Altered Molecular Association of Heterologous PrPSc with PrPC

“…The former is distinguished from the latter by its insolubility in nonionic detergents and relative resistance to proteinase K (PK) 2 digestion (1). Once generated, PrP Sc propagates by templating its conformation onto PrP C , leading to the accumulation of PrP Sc and associated central nervous system pathologic features of neuronal death, gliosis, and vacuolation (2). The PrP ScPrP C interface has not been resolved, although a specific orientation is predicted, based on several lines of evidence suggesting that sequence homology between PrP Sc and PrP C at key sites within the molecule are necessary for effective propagation of PrP Sc , a feature that forms the basis for the well recognized species barrier to prion transmission (3).…”