What are Prions?

Definition

• Prion: Coined to mean "proteinaceous infectious particle."
• Pronunciation: PREE-on (U.S.), PRY-on (U.K.).
• Misfolded proteins that can spread by inducing other proteins to misfold.

Historical Background

• Scrapie:

  • A disease in sheep, noted for symptoms like scraping hindquarters raw.
  • Spread like a virus but exhibited characteristics of a genetic disease.
  • Infectious agent was nearly indestructible, surviving high temperatures.

• Kuru:

  • Neurological disease epidemic in Papua New Guinea.
  • Transmission to chimpanzees demonstrated by Carleton Gajdusek, Nobel Prize 1976.
  • Damage resembles that of Creutzfeldt-Jakob disease (CJD) and scrapie.

Discovery of Prions

• Stanley Prusiner:

  • Demonstrated the infectious agent of scrapie was a protein.
  • No DNA or RNA, a novel concept in biology.
  • Won the Nobel Prize in 1997 for this discovery.

• Prion Protein (PrP):

  • Prusiner discovered the protein of prions, called prion protein (PrP).
  • PrP is present in all individuals, with the PRNP gene on chromosome 20 encoding it.

Mechanism of Disease

• Prion Protein Conversion:

  • Normal state: Cellular prion protein (PrPC).
  • Disease state: Scrapie prion protein (PrPSc).
  • PrPSc can convert PrPC into PrPSc.

• Analogy:

  • PrPSc acts like "ice-nine" from Kurt Vonnegut’s novel, converting other proteins into the disease state.

Prion Diseases

• Initially Known Diseases:

  • Kuru, Scrapie, Creutzfeldt-Jakob Disease (CJD).
  • Caused by PrP.

• Other Prion Diseases:

  • Mad cow disease (bovine spongiform encephalopathy).
  • Chronic wasting disease in deer.
  • Fatal familial insomnia and Gerstmann-Straussler-Scheinker syndrome in humans.

• Broader Implications:

  • Other neurodegenerative diseases (Alzheimer’s, Parkinson’s) may involve similar protein misfolding.
  • In yeast, prions may play a beneficial role in survival.

Terminology and Focus

• Prion Diseases at Prion Alliance:
  • Primarily focus on misfolded PrP particles causing CJD, fatal familial insomnia, etc.

Further Reading

• Recommended: The Family That Couldn't Sleep by D.T. Max (2006)

These notes provide a condensed overview of prions, their discovery, their role in various diseases, and the broader implications of protein misfolding in biology.