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Prion disease

From Wikipedia
transmissible spongiform encephalopathy
designated intractable/rare disease, rare disease, class of disease
Subclass ofencephalopathy, neurodegenerative disease with dementia Edit
Has causeprion Edit
Health specialtyinfectious diseases Edit
Genetic associationPRNP, SEMA3A Edit
External data available at URLhttp://www.nanbyou.or.jp/entry/5370 Edit
ICD-9-CM046.19 Edit
NCI Thesaurus IDC27585, C128346 Edit

Transmissible spongiform encephalopathies (TSEs), dem sanso know as prion diseases,[1] be a group of progressive, incurable, den invariably fatal conditions wey be associated plus de degeneration of de nervous system insyd chaw animals, wey dey include humans, cattle, den sheep. Strong evidence dey support de once unorthodox hypothesis wey prion diseases be transmitted by abnormally shaped protein molecules dem know as prions.[2][3] Prions dey consist of a protein dem call de prion protein (PrP).[2] Misshapen PrP (dem often refer to as PrPSc) dey conveys ein abnormal structure to native PrP molecules by a crystallization-like seeding process. Because de abnormal proteins stick to each oda, den secof PrP be continuously produced by cells, PrPSc wey accumulate insyd de brain, dey harm neurons den eventually dey cause clinical disease.[2][3][4]

Prion diseases be marked by mental den physical deterioration wey dey worsen over time.[5][6] A defining pathologic characteristic of prion diseases be de appearance of small vacuoles insyd various parts of de central nervous system wey dey create a sponge-like appearance wen na brain tissue obtain at autopsy be examined under a microscope.[2][3] Oda changes insyd affected regions dey include de buildup of PrPSc, gliosis, den de loss of neurons.[7]

Insyd non-human mammals, de prion diseases dey include scrapie insyd sheep, bovine spongiform encephalopathy (BSE) insyd cattle (dem popularly know as "mad cow disease") chronic wasting disease (CWD) insyd deer den elk, den odas.[8] Prion diseases of humans dey include Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, kuru, den variably protease-sensitive prionopathy.[6][9] Na dem divide Creutzfeldt-Jakob disease into four subtypes: sporadic (idiopathic) (sCJD), hereditary/familial (fCJD), iatrogenic (iCJD) den variant (vCJD). Dese diseases dey form a spectrum of related conditions plus overlapping signs den symptoms.

Prion diseases be unusual insyd dat dema etiology fi be genetic, infectious, anaa idiopathic.[2] Genetic (inherited) prion diseases dey result from rare mutations insyd PRNP, de gene wey dey codes for PrP (spy Genetics, below). Unlike conventional infectious diseases, wich be spread by agents plus a DNA anaa RNA genome (such as viruses anaa bacteria), prion diseases be transmitted by prions, de active material of wich be solely abnormal PrP. Infection fi occur wen de organism be exposed to prions thru ingestion of infected foodstuffs anaa via iatrogenic means (such as treatment plus biologic material wey na e be inadvertently contaminated plus prions).[10] De variant form of Creutzfeldt–Jakob disease insyd humans be caused by exposure to BSE prions.[11][12][13] Whereas de naturally occurring transmission of prion diseases among nonhuman species be relatively common, prion transmission to humans be very rare; rather, de majority of human prion diseases be idiopathic insyd nature[14] (spy Infectivity, below). Sporadic prion diseases dey occur insyd de absence of a mutation insyd de gene for PrP anaa a source of infection.

Although na research show say de infectious capacity of prions be encoded insyd de conformation of PrPSc,[2][4] e be likely say auxiliary substances contribute to dema formation den/anaa infectivity. Purified PrPC dey appear to be unable to convert to de infectious PrPSc form insyd a protein misfolding cyclic amplification (PMCA) assay unless dem add oda components, such as a polyanion (usually RNA) den lipids. Dese oda components, dem term cofactors, fi form part of de infectious prion, anaa dem fi serve as catalysts give de replication of a protein-only prion.[15] Considering say na de cofactors fi be produced by chemical synthesis instead of dem be sourced solely from infected cases (anaa any animal at all), e be fair to say dat dem no dey form de infectious part of de prion. However, dese catalysts (especially de polyanion) get a tendency to be included insyd de prion aggregate, wich dey make seeding new aggregates easier in vitro.[16][17]

References

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  1. ↑ "Transmissible Spongiform Encephalopathies". National Institute of Neurological Disorders and Stroke (in English). Retrieved 23 April 2023.
  2. 1 2 3 4 5 6 Prusiner, S. B. (10 November 1998). "Prions". Proceedings of the National Academy of Sciences of the United States of America. 95 (23): 13363–13383. Bibcode:1998PNAS...9513363P. doi:10.1073/pnas.95.23.13363. PMC 33918. PMID 9811807.
  3. 1 2 3 Wadsworth JD, Collinge J (August 2010). "Molecular pathology of human prion disease". Acta Neuropathologica. 121 (1): 69–77. doi:10.1007/s00401-010-0735-5. PMC 3015177. PMID 20694796.
  4. 1 2 Aguzzi A, Calella AM (2009). "Prions: protein aggregation and infectious diseases". Physiology Reviews. 89 (4): 1105–1152. doi:10.1152/physrev.00006.2009. PMID 19789378.
  5. ↑ Chesebro, Bruce (June 2003). "Introduction to the transmissible spongiform encephalopathies or prion diseases". British Medical Bulletin. 66 (1): 1–20. doi:10.1093/bmb/66.1.1. PMID 14522845.
  6. 1 2 Wadsworth JD, Collinge J (2007). "Update on human prion disease". Biochim Biophys Acta. 1772 (6): 598–609. doi:10.1016/j.bbadis.2007.02.010. PMID 17408929.
  7. ↑ Ritchie DL, Smith C (2025). "Pathological spectrum of sporadic Creutzfeldt-Jakob disease". Pathology. 57 (2): 196–206. doi:10.1016/j.pathol.2024.09.005. PMID 39665904.
  8. ↑ Imran M, Mahmood S (November 2011). "An overview of animal prion diseases". Virology Journal. 8 493. doi:10.1186/1743-422X-8-493. PMC 3228711. PMID 22044871.
  9. ↑ Ironside JW, Ritchie DL, Barria MA (2017). "Prion diseases". Neuropathology. Handbook of Clinical Neurology. Vol. 145. pp. 393–403. doi:10.1016/B978-0-12-802395-2.00028-6. ISBN 978-0-12-802395-2. PMID 28987186.
  10. ↑ Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, d'Aignaux JH, Cervenakova L, Fradkin J, Schonberger LB, Collins SJ (2000). "Iatrogenic Creutzfeldt–Jakob disease at the millennium". Neurology. 55 (8): 1075–81. doi:10.1212/WNL.55.8.1075. PMID 11071481.
  11. ↑ "Variant Creutzfeldt-Jakob disease". World Health Organization. Retrieved 2017-04-25. February 2012. Archived from the original on December 20, 2002.
  12. ↑ "About Variant Creutzfeldt-Jakob Disease (vCJD)". CDC. 12 November 2024.
  13. ↑ Collinge, John; Sidle, Katie C. L.; Meads, Julie; Ironside, James; Hill, Andrew F. (October 1996). "Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD". Nature. 383 (6602): 685–690. Bibcode:1996Natur.383..685C. doi:10.1038/383685a0. PMID 8878476.
  14. ↑ Ritchie DL, Barria MA (2021). "Prion Diseases: A Unique Transmissible Agent or a Model for Neurodegenerative Diseases?". Biomolecules. 11 (2): 207. doi:10.3390/biom11020207. PMC 7912988. PMID 33540845.
  15. ↑ Lee KS, Caughey B (2007). "A simplified recipe for prions". Proceedings of the National Academy of Sciences USA. 104 (23): 9551–9552. Bibcode:2007PNAS..104.9551L. doi:10.1073/pnas.0703910104. PMC 1887566. PMID 17535888.
  16. ↑ Geoghegan, James C.; Valdes, Pablo A.; Orem, Nicholas R.; Deleault, Nathan R.; Williamson, R. Anthony; Harris, Brent T.; Supattapone, Surachai (December 2007). "Selective Incorporation of Polyanionic Molecules into Hamster Prions". Journal of Biological Chemistry. 282 (50): 36341–36353. doi:10.1074/jbc.M704447200. PMC 3091164. PMID 17940287.
  17. ↑ Shaked, GM; Meiner, Z; Avraham, I; Taraboulos, A; Gabizon, R (27 April 2001). "Reconstitution of prion infectivity from solubilized protease-resistant PrP and nonprotein components of prion rods". The Journal of Biological Chemistry. 276 (17): 14324–8. doi:10.1074/jbc.M007815200. PMID 11152454.
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