Prion disease;
Creutzfeldt-Jacob disease (CJD);
Gerstmann-Straussler disease (GSD);
Gerstmann-Straussler-Scheinker disease (GSSD);
Fatal familial insomnia (FFI)

Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC.

Neurodegenerative disease

nt06465 Prion disease
nt06466 Pathways of neurodegeneration
nt06534 Unfolded protein response

PRNP (mutation) [HSA:5621] [KO:K05634]

Affected region: cerebral cortex, thalamus, brain stem, cerebellum, etc.
Microscopic lesion: prion plaques

PMID:14744440