Prion

For the bird, see Prion (bird). For the theoretical subatomic particle, see Preon.
Not to be confused with Major prion protein.

Prion
3D structure of major prion protein
Pronunciation
SpecialtyInfectious diseases

A prion /ˈpriːɒn/ ⓘ is a misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), which are fatal and transmissible neurodegenerative diseases affecting both humans and animals.[3][4] These proteins can misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein, leading to an abnormal three-dimensional structure that can propagate misfolding in other proteins.[5]

The term prion comes from "proteinaceous infectious particle".[6][7] Unlike other infectious agents such as viruses, bacteria, and fungi, prions do not contain nucleic acids (DNA or RNA). Prions are mainly twisted isoforms of the major prion protein (PrP), a naturally occurring protein with an uncertain function. They are the hypothesized cause of various TSEs, including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (mad cow disease), and Creutzfeldt–Jakob disease (CJD) in humans.[8]

All known prion diseases in mammals affect the structure of the brain or other neural tissues. These diseases are progressive, have no known effective treatment, and are invariably fatal.[9] Most prion diseases were thought to be caused by PrP until 2015 when a prion form of alpha-synuclein was linked to multiple system atrophy (MSA).[10] Prions are also linked to other neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), which are sometimes referred to as prion-like diseases.[11][12]

Prions are a type of intrinsically disordered protein that continuously changes conformation unless bound to a specific partner, such as another protein. Once a prion binds to another in the same conformation, it stabilizes and can form a fibril, leading to abnormal protein aggregates called amyloids. These amyloids accumulate in infected tissue, causing damage and cell death.[13] The structural stability of prions makes them resistant to denaturation by chemical or physical agents, complicating disposal and containment, and raising concerns about iatrogenic spread through medical instruments.

  1. ^ "English pronunciation of prion". Cambridge Dictionary. Cambridge University Press. Archived from the original on April 24, 2017. Retrieved March 30, 2020.
  2. ^ "Definition of Prion". Dictionary.com. Random House, Inc. 2021. Definition 2 of 2. Archived from the original on September 12, 2021. Retrieved September 12, 2021.
  3. ^ "Transmissible Spongiform Encephalopathies". National Institute of Neurological Disorders and Stroke. Retrieved April 23, 2023.
  4. ^ "Prion diseases". Diseases and conditions. National Institute of Health. Archived from the original on May 22, 2020. Retrieved June 20, 2018.
  5. ^ Kumar V (2021). Robbins & Cotran Pathologic Basis of Disease (10th ed.).
  6. ^ "What Is a Prion?". Scientific American. Archived from the original on May 16, 2018. Retrieved May 15, 2018.
  7. ^ "Prion infectious agent". Encyclopaedia Britannica. Archived from the original on May 16, 2018. Retrieved May 15, 2018.
  8. ^ Prusiner SB (June 1991). "Molecular biology of prion diseases". Science. 252 (5012): 1515–1522. Bibcode:1991Sci...252.1515P. doi:10.1126/science.1675487. PMID 1675487. S2CID 22417182.
  9. ^ Prusiner SB (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.
  10. ^ Cite error: The named reference pmid26324905 was invoked but never defined (see the help page).
  11. ^ Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (February 2009). "Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers". Nature. 457 (7233): 1128–1132. Bibcode:2009Natur.457.1128L. doi:10.1038/nature07761. PMC 2748841. PMID 19242475.
  12. ^ Olanow CW, Brundin P (January 2013). "Parkinson's disease and alpha synuclein: is Parkinson's disease a prion-like disorder?". Movement Disorders. 28 (1): 31–40. doi:10.1002/mds.25373. PMID 23390095. S2CID 38287298.
  13. ^ Dobson CM (February 2001). "The structural basis of protein folding and its links with human disease". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 356 (1406): 133–145. doi:10.1098/rstb.2000.0758. PMC 1088418. PMID 11260793.