Molecular Pathology of Human Prion Diseases

Abstract

Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP) to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant diseaseassociated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

The diversities of PrPSc distributions and pathologic changes in various brain regions from a Chinese patient with G114V genetic CJD

“…Those diversities are closely linked with the specific mutations in PRNP and are controlled by the polymorphism of codon 129. 4 However, possibly due to infrequent incidence, many types of gCJD lack detailed description.…”

Infection-Associated Dementia

“…5 Prion protein bentuk patogenik (PrP Sc ) memiliki gugus glycosylphosphatidylinositol (GPI) yang memfasilitasi melekatnya prion protein pada membran sel neuron. 13,19 Plasmodium falciparum dalam eritrosit terinfeksi mampu menghasilkan protein antigenik Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) yang memediasi terjadinya cytoadherence.…”

Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris

“…Misfolded isoforms of PrP mediate the intra- and inter-species transmission of the mammalian prion diseases (transmissible spongiform encephalopathies, TSEs) (Kovacs and Budka 2009). Copper binding to PrP occurs extracellularly at the N -terminal domain, which in most mammals contains five or six repeats of a peptide of eight or nine residues with the consensus sequence P(Q/H)GGG(G/-)WGQ (Wopfner et al 1999; van Rheede et al 2003; Acutis et al 2007).…”