Human Sporadic Prion Diseases

摘要: Sporadic prion diseases account for approximately 85% of all human diseases. They include sporadic Creutzfeldt–Jakob disease (sCJD), which affect over 90% the cases, as well fatal insomnia (sFI) and variably protease-sensitive prionopathy (VPSPr), 1–2% 3–4% respectively. CJD comprises five phenotypically distinct subtypes most are associated with molecular features. The signature each subtype is determined by pairing genotype at methionine/valine polymorphic codon 129 protein (PrP) gene either one two disease-associated PrP (PrPDis) types characterized physico-chemical characteristics. VPSPr may three similarly whereas no known in sFI. Currently, likely etiological-pathogenetic mechanism failure quality control complex permitting presence conformationally abnormal pathogenic variants capable converting normal into conformers. These conformers then propagate damage vulnerable tissues they populate. Essentially same sequence basic events play out other forming amyloids such Alzheimer’s major neurodegenerative type 2 diabetes amyloid A (AA).