Truncated forms of the human prion protein in normal brain and in prion diseases.

摘要: The cellular form of the prion protein (PrPc) is a glycoprotein anchored to cell membrane by glycosylphosphatidylinositol moiety. An aberrant PrPc that partially resistant proteases, PrPres, hallmark diseases, which in humans include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia. We have characterized major forms PrP normal pathological human brains. A COOH-terminal fragment PrPc, designated C1, abundant CJD brains as well neuroblastoma cells. Sequence analysis revealed C1 contains alternative NH2 termini starting at His-111 or Met-112. Like glycosylated, membrane, heat-stable. Consistent with lack NH2-terminal region more acidic than does not bind heparin. additional longer C2, present substantial amounts C2 proteases detergent-insoluble. Our data indicate product metabolism, generated cleavage disrupts neurotoxic amyloidogenic comprising residues 106-126. This remains intact suggesting role for diseases.