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INTRODUCTION

Prions are infectious proteins that cause neurologic disease.Unlike other infectiousparticles, they do not have a genome andare composed only ofprotein, but different strains exist that allow for very little cross-species infection. They multiply by causing a constitutively expressed host protein, PrPc, to fold into another conformation, PrPsc. PrPc is normally present inhumans and other mammals in the highest concentration in the lipid rafts of central nervous system neurons. Its function is unknown, but because PrPc is widely conserved evolutionarily across species, it may play an important Mind falling apartneuroprotective role in signal transduction. PrPc and PrPsc have the same amino acid sequence, but they are different isoforms with different secondary, tertiary, and quaternary structure. Through Fourier-transformed infrared spectroscopy, researchers have observed that PrPc has more alpha-helix content (40%), very little beta-sheet structures (~0%) and can exist in monomer form. PrPsc has less alpha-helix content (30%), many more beta-sheet structures (45%), and rarely exists in monomer form.

PrPc is necessary for PrPsc infection, but nothing is known for certain about routes of infection. Several models describing the mechanism that PrPsc induces PrPc structural change have been hypothesized: template-assisted conversion, nucleation/polymerization model, and assisted-nucleation model. PrPsc infection is limited by a species barrier, because transforming PrPc is easier when the amino acid sequence is the same as the infectious PrPsc.

Until the patient shows signs of neurologic dysfunction, diagnosis of a prion infection is difficult. After clinical signs are apparent, tissue diagnosis methods such as histologic evaluation, immunohistochemistry, and conformation-dependent immunoassays are used to confirm the assessment. Prion disease affect mammals and some fungi. In non-humans, scrapie, a prion infection in sheep, was first documented in 1732, and bovine spongiform encephalopathy (BSE) was first reported in 1986 (complete timeline here). In humans, a mysterious neurologic affliction, Kuru, was documented among the Fore people, whose culture extends to the practice of eating the brains of their dead. Other human prion infections include Creutzfield-Jakob Disease (sporadic CJD, iatrogenic CJD, variant CJD, familial CJD), Gerstmann-Straussler-Scheinker Disease, fatal insomnia (familial- FFI and sporadic – SFI). vCJD, or “Mad Cow” is arguably the most renowned of the human prion diseases, even though it only causes < 1% of all CJD cases.

 

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