Prion diseases protein-only hypothesis

The central dogma of molecular biology has traditionally posited that nucleic acids alone function as genetic determinants because these macromolecules can template their own replication. The prion or protein-only hypothesis expands the central dogma to include proteins as etiologic agents for disease transmission (Griffith, 1967 Prusiner 1982) and elements of inheritance for phenotypic traits (Wickner, 1994). Prions are unique proteins that can exist in more than one stable conformation, and at least one of these states can be transmitted to newly synthesized protein as a form of templated replication. Since each physical state is associated with a distinct phenotypic state, the trait becomes heritable. 

Keywords Creutzfeldt Jakob disease Fatal insomnia Gerstmann-Straussler-Scheinker Kuru Neuroinvasion Prion Protein-only hypothesis. 

TSEs can exhibit inherited, infectious and sporadic presentations. Additionally, the inherited disease can also be infectious. CJD occurs both as an inherited autosomal dominant disorder and in a transmissible form. In the protein only hypothesis, the abnormal prion protein, either introduced from external sources or produced by the mutated prion protein gene, affects normal protein folding and shifts the prion protein folding towards the formation... 

Like other neurodegenerative disorders, such as Alzheimer s and Parkinson s disease, prion diseases are characterized by the formation and accumulation of an aberrantly folded protein in the brain. However, a unique feature of prion diseases is their transmissibility. Prions (acronym for proteinaceous infectious particles) are mainly composed of PrPSc, polysaccharides, and lipids, but lack nucleic acids longer than 25 nucleotides, arguing against an essential role for DNA/RNA in mediating infectivity [35, 36]. Indeed, recent experiments support the protein-only hypothesis recombinant PrP expressed in and purified from bacteria and subsequently misfolded in vitro can transmit the disease [37-40]. 

The fact that all forms of inherited human prion diseases known so far are linked with dominant mutations in the gene encoding human PrP has been used as a strong argument in favor of the protein-only hypothesis, as the infectious prion agent spontaneously develops in affected individuals (for reviews, see Prusiner, 1997 Prusiner et al,... 

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