Rational targeting for prion therapeutics

Nat Rev Neurosci. 2005 Jan;6(1):23-34. doi: 10.1038/nrn1584.


Prions--pathogens that are lethal to humans and other animals--are thought to be conformational isomers of the cellular prion protein. Their unique biology, and the potential for a wider pathobiological significance of prion-like mechanisms, has motivated much research into understanding prion neurodegeneration. Moreover, concerns that extensive dietary exposure to bovine spongiform encephalopathy (BSE) prions might have infected many individuals--who might eventually develop its human counterpart, variant Creutzfeldt-Jakob disease (vCJD)--has focused much interest on therapeutics. The challenge of interrupting this aggressive, diffuse and uniformly fatal neurodegenerative process is daunting. However, the recent finding that the onset of clinical disease in established neuroinvasive prion infection in a mouse model can be halted and early pathology reversed is a source for considerable optimism. A therapeutic focus on the cellular prion protein, rather than prions themselves, which might not be directly neurotoxic, is suggested.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Prion Diseases / drug therapy
  • Prion Diseases / genetics
  • Prion Diseases / metabolism*
  • Prions / antagonists & inhibitors
  • Prions / genetics
  • Prions / metabolism*


  • Prions