Prion Propagation: Difference between revisions

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==References==
==References==
[Sample reference] [http://ijs.sgmjournals.org/cgi/reprint/50/2/489 Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "''Palaeococcus ferrophilus'' gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". ''International Journal of Systematic and Evolutionary Microbiology''. 2000. Volume 50. p. 489-500.]
[Sample reference] [http://ijs.sgmjournals.org/cgi/reprint/50/2/489 Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "''Palaeococcus ferrophilus'' gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". ''International Journal of Systematic and Evolutionary Microbiology''. 2000. Volume 50. p. 489-500.]
[http://journals.ohiolink.edu/ejc/pdf.cgi/Hill_Andrew_F.pdf?issn=00068950&issue=v126i0006&article=1333_mcoscd Andrew F. Hill, Susan Joiner, Jonathan D. F. Wadsworth, Katie C. L. Sidle, Jeanne E. Bell, Herbert Budka, James W. Ironside and John Collinge, "Molecular classification of sporadic Creutzfeldt-Jakob disease".  ''Brain''. 2003.  Volume 126.  p. 1333-1346.]


Edited by student of [mailto:slonczewski@kenyon.edu Joan Slonczewski] for [http://biology.kenyon.edu/courses/biol238/biol238syl09.html BIOL 238 Microbiology], 2009, [http://www.kenyon.edu/index.xml Kenyon College].
Edited by student of [mailto:slonczewski@kenyon.edu Joan Slonczewski] for [http://biology.kenyon.edu/courses/biol238/biol238syl09.html BIOL 238 Microbiology], 2009, [http://www.kenyon.edu/index.xml Kenyon College].

Revision as of 00:55, 16 April 2009

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. CJD cannot be absolutely diagnosed until a post mortem autopsy, but symptoms may begin as late in life as 60, and spinal taps and EEGs can rule out other forms of treatable dementia. Symptoms include progressively worsening dementia, loss of memory and muscle functions, myoclonus (muscle jerks), and even blindness, leading into a comatose state which is often accompanied by a form of pneumonia. Patients usually die within a single year of onset of symptoms. There is no cure or treatment for the disease as of 2009.

The sporadic mutation of the PRNP gene, caused by rare genetic event or somatic mutation, seems to be focused on amino acid 129. Several different classifications of the PrPSc have been primarily identified by differential cleavage patterns by proteinase K. These types have been additionally separated based on amino acid sequence with respect to a valine or methionine at position 129 in the PrPSc protein, and by location and formation of plaques in different regions of the brain. Type 1 PrPSc is characterized by homozygous methionine (MM) at codon 129, and synaptic plaque formation primarily in the cerebral cortex and occipital lobe. Type 2 PrPSc can be homozygous methionine, valine (VV), or heterozygous (MV), and causes mainly perivacuolar plaque formation in the basal ganglia and cerebellum in addition to the cerebral cortex. Type 3 PrPSc is characterized by MV or VV at codon 129, and show linear plaque formation similar to that of the kuru prion, located mainly in the basal ganglia and cerebellum. Type 4 PrPSc (MM)was associated mainly with the vCJD prion, which evidence points toward hereditary transmission of the isoform mutation.

Acquired Propagation: Kuru


Include some current research in each topic, with at least one figure showing data.

Inherited Propagation: Fatal Familial Insomnia


Include some current research in each topic, with at least one figure showing data.

Conclusion


Overall paper length should be 3,000 words, with at least 3 figures.

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Andrew F. Hill, Susan Joiner, Jonathan D. F. Wadsworth, Katie C. L. Sidle, Jeanne E. Bell, Herbert Budka, James W. Ironside and John Collinge, "Molecular classification of sporadic Creutzfeldt-Jakob disease". Brain. 2003. Volume 126. p. 1333-1346.

Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.