neurologic disorders
Overview of Prion Diseases
Introduction
Prion diseases are progressive, fatal, and untreatable degenerative brain disorders. Prominent types of prion diseases include Creutzfeldt-Jakob Disease (CJD) (CJD), the prototypic example (usually sporadic) Variant CJD (vCJD) (vCJD; acquired by eating prion-contaminated beef) Variably Protease-Sensitive Prionopathy (VPSPr) (VPSPr; sporadic) Gerstmann-Sträussler-Scheinker Disease (GSS) (GSS; inherited) Fatal Insomnia (FI; includes a sporadic and an inherited form) Kuru (acquired by ritual cannibalism) A recently identified type is Prion Disease Associated With Diarrhea and Autonomic Neuropathy , which is inherited. Prion diseases result from misfolding of a normal cell-surface brain protein called cellular prion protein (PrPC), whose exact function is unknown. Misfolded prion proteins are called prions or scrapie PrP (PrPSc—from the name of the prototypic prion disease of sheep). Prions (PrPSc) are pathogenic and transmissible. They produce prion disease by Self-replicating: PrPScinduces conformational transformation of PrPC, creating duplicate PrPSc, which, in a chain reaction, induces further transformation of PrPCinto PrPSc. This transformation process spreads PrPScto various regions of the brain. Causing neuronal cell death Normal PrPCis water soluble and protease sensitive, but a large percentage of PrPScis water insoluble and markedly resistant to protease degradation (similar to beta-amyloid in Alzheimer disease, which PrPScresembles), resulting in slow but inexorable cellular accumulation and neuronal cell death. Accompanying pathologic changes include gliosis and characteristic histologic vacuolar (spongiform) changes, resulting in dementia and other neurologic deficits. In acquired prion diseases, symptoms and signs develop months to years after the initial exposure to PrPSc. Prion diseases should be considered in all patients with dementia, especially if it progresses rapidly. 