Prions

• Prions are infectious proteins which invariably cause fatal neurodegenerative diseases and are mediated by an entirely novel mechanism. They may present as genetic, infectious, or sporadic disorders.
• Prions are made of a protein called PrP. PrP is found in cells throughout the body of health mammals. PrPC, a strain of PrP, is associated with a cells plasma membrane. It is highly conserved across animal species and has various functions to do with immune responses, signal transduction, copper binding, synaptic transmission, and apoptotic functions.
• Prions cause ‘misfolding’ of PrPC structure which causes profound changes in the physicochemical properties of the protein.
• As more PrPC is converted into PrPSc molecule gradually accumulates. Aggregations are abnormal and the PrPSc form amyloid fibers which accumulate into plaques. These are particularly in long lived cells of the CNS, which leads to neural apoptosis, synaptic dysfunction and neurodegeneration.
• Prions themselves not directly neurotoxic, but misfolded proteins and amyloid deposits likely are.
• Different prion strains exist which cause distinct disease characteristics. This diversity is caused by conformation and glycosylation patterns of PrPSc. The strain differentiation is based on:

  • incubation periods
  • mortality patterns
  • PrPSc distribution patterns
  • lesion profiles
  • proteinase K sensitivity