Prions

Background

• Proteinaceous infectious particles that are capable of self-propagating
• May be acquired by infection (iCJD and vCJD), sporadic mutation (sCJD and sFI), or heritable genetics (fCJD, GSS, and FFI)
• See also Creutzfeld-Jakob disease

Disease	Abbr	Host	Etiology
Human Prion Diseases
Kuru	—	human	ritualistic cannibalism in Papua New Guinea
sporadic Creutzfeld-Jakob disease	sCJD	human	spontaneous mutation of PrPC to PrPSc
familial Creutzfeld-Jakob disease	fCJD	human	mutations in PRNP gene
Gerstmann-Straüssler-Scheinker syndrome	GSS	human	mutations in PRNP gene
iatrogenic Creutzfeld-Jakob disease	iCJD	human	infection from surgical exposure to sCJD
fatal familial insomnia	FFI	human	PRNP haplotype 178N-129M
variant Creutzfeld-Jakob disease	vCJD	human	BSE origin
sporadic fatal insomnia	sFI	human	spontaneous mutation of PrPC to PrPSc
variably protease-sensitive prionopathy	VPSPr	human	spontaneous mutation of PrPC to PrPSc
Animal Prion Diseases
scrapie	—	sheep and goats	unknown origin
transmissible mink encephalopathy	TME	mink	sheep or cattle origin
chronic wasting disease	CWD	cervids	unknown origin
bovine spongiform encephalopathy	BSE	cattle	unknown origin
exotic ungulate spongiform encephalopathy	EUE	Nyala, Kudu	BSE origin
feline spongiform encephalopathy	FSE	cats	BSE origin
non-human primate spongiform encephalopathy	NHP	lemurs	BSE origin

Pathophysiology

• Most caused by mutations of the prion protein, PrP, which is encoded by the PRNP gene
  • PrP^C is the cellular, regular isoform PrP^Sc is prion-disease-causing mutation
• Accumulation of misfolded PrP^Sc causes the symptoms