Prion Propagation
Prions are unique infectious agents that consist only of a protein, and are not replicated via nucleic acid. The wild type protein PrPc (Prion-related Protein) consisting of approximately 209 amino acids in primarily alpha-helix secondary structures with one disulfide bond, is expressed throughout the body, although the function is unknown. However, due to a mutation in the PRNP gene sequence, the amino acid sequence, or error in posttranslational protein folding, the PrPc protein is misfolded into an isoform PrPsc, which consists of mainly beta-sheet fibrillar secondary structures that tend to aggregate, also known as a form of amyloid. This alteration in secondary structure leads to accumulation of PrPsc, formation of plaques, and prion diseases such as Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, kuru, Transmissible Spongiform Encephalopathy (TSE), Bovine Spongiform Encephalopathy (BSE or "mad cow" disease), scrapie, and Familial Fatal Insomnia (FFI). Since the aggregates are formed from native protein sequences, no immune response is raised, and since the plaques are non-standard, they are semi-resistant to proteinase K (PK) degradation.
The Prion Hypothesis
The prion hypothesis, which states that prions propagate themselves without nucleic acid involvement, is controversial because it contradicts the fundamental tenet of molecular biology: proteins are translated from RNA which is transcribed from DNA. However, while the precise mechanism of prion propagation is unclear, there is much evidence to support the theory that PrPsc is the primary, if not sole agent responsible for propagation of more PrPsc. Different hypotheses of this interaction exist, most of which involve the PrPsc protein acting as a template to induce misfolding of PrPc, or a mysterious as-yet unidentified “protein X”, which binds one unit of PrPc and one unit of PrPsc together in a complex. Three known classes of prion propagation have been identified as distinct, including sporadic, acquired, and inherited PrPsc accumulation.
Sporadic Propagation: Creutzfeldt-Jakob disease
CJD is classified as a neuropathological disorder cause by sporadic prion propagation, although there is evidence for a new form, variant-CJD or vCJD, that is hereditary. The sporadic mutation of the PRNP gene, caused by rare genetic event or somatic mutation
Acquired Propagation: Kuru
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Inherited Propagation: Fatal Familial Insomnia
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Conclusion
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References
Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.
