PRNP

About PRNP

PRNP on chromosome 20p13 encodes the prion protein, PrP, a cell surface glycoprotein anchored to the membrane and highly expressed in neurons, whose normal function remains incompletely understood. Misfolded PrP, called PrPSc, can template the misfolding of normal PrP, producing transmissible spongiform encephalopathies. Stanley Prusiner received the 1997 Nobel Prize for proposing that prions are infectious proteins. Human prion diseases are sporadic in most cases, mainly sporadic Creutzfeldt Jakob disease, genetic in roughly 10 to 15 percent, and acquired in a small minority, through variant CJD linked to bovine spongiform encephalopathy, kuru linked to ritual funerary practices in Papua New Guinea, and iatrogenic transmission through cadaveric growth hormone or dura mater grafts. Genetic prion diseases include familial CJD, Gerstmann Straussler Scheinker syndrome, and fatal familial insomnia. The D178N variant causes fatal familial insomnia when it occurs with methionine at codon 129 on the same allele, and familial CJD when it occurs with valine. E200K is the most common variant causing familial CJD, with clusters among Libyan Jewish people and in Slovakia. The common codon 129 polymorphism influences susceptibility and disease features. Prion diseases cause rapidly progressive dementia, myoclonus, and ataxia, and they are invariably fatal. Mice lacking PrP are resistant to prion infection, supporting PrP lowering drugs, which are in clinical trials.