Prion Diseases

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are transmissible degenerative disorders of the central nervous system in mammals. TSEs are fatal and are caused by the proteinaceous infectious particles, termed prions that lack informational nucleic acids. TSEs include Creutzfeldt–Jakob disease in humans, scrapie in sheep, bovine spongiform encephalopathy or ‘mad cow disease’ in cattle and chronic wasting disease in deer and elk. These diseases manifest spongiform degeneration, reactive gliosis, and deposition of prion aggregates in the brain. The aetiology of TSEs is sporadic, genetic, or acquired. The primary structure of PrP^C, conformational diversity of PrP^Sc, and their interplay influence intra- and inter-species prion transmission. The role of lymphoreticular system is pivotal in early prion pathogenesis and neuroinvasion, whereas neuronal damage caused by prion infection could be achieved by several different mechanisms. Despite the potential risk for public health, diagnosis and therapy for prion diseases are currently unavailable.

Key Concepts:

• Prion diseases represent a group of human and animal diseases that include sporadic, inherited, and acquired Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), and fatal familial insomnia (FFI) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, feline spongiform encephalopathy (FSE) in cats, and exotic ungluate encephalopathy (EUE) in exotic ungulates.
  
• Prion diseases are fatal neurological disorders and caused by the unconventional proteinaceous pathogen, termed prion.
  
• Prion diseases manifest characteristic clinical and neuropathological features.
  
• Prion diseases are transmissible within and between the species.
  
• Transmission of prion diseases is determined by the amino acid sequence variability of PrP^C and prion strains conferred by conformational diversity of PrP^Sc.
  
• The lymphoreticular system is crucial in prion pathogenesis and neuroinvasion.
  
• Gain of pathologic PrP^Sc function and/or loss of neuroprotective PrP^C function facilitate neuronal damages in the central nervous system by direct or indirect mechanism associated with astrocyte and microglial cells.
  
• Atypical TSEs and human-to-human transmission of vCJD have been identified.
  
• Diagnosis and therapy for prion disease are not available.
  

Keywords: prion; PrP^Sc; PrP^C; TSE; CJD; Scrapie; BSE; CWD; TME; atypical TSE