The Science of Prion Diseases
The normal cellular prion protein, denoted PrPC (see schematic representation of its molecular structure below), is found in most cell types within the body. In disease, this protein undergoes a structural transition to its disease-causing form (PrPSc) with profoundly different physicochemical properties. One of these properties is a resistance to the digestion by enzymes that normally break down proteins.
The conversion of PrPC to PrPSc appears to require localization of PrPC to lipid rafts, specialized cellular membrane regions rich in a subset of cellular lipids such as cholesterol. However, the precise physiological environment which hosts this event remains elusive. In all familial cases of prion disease the above aberrant processes can be linked to the presence of a mutation in the human gene which encodes the prion protein.
Pathology and clinical manifestation
Prion diseases are characterized by the aggregation of PrPSc within the central nervous system. These aggregates can be visualized with specific stains (such as Congo Red stain) and are often referred to “plaques”. The toxic accumulation of PrPSc in turn causes the formation of large intracellular holes (vacuole formation) and neuronal death. Together these morphological changes create a sponge-like appearance of the brain tissue (the reason why prion diseases are sometimes referred to as Transmissible Spongiform Encephalopathies (TSEs)). Other histological changes include an increase in star-shaped non-neuronal cells (astrogliosis) and the conspicuous absence of an overt inflammatory reaction.
The incubation period for prion diseases generally extends over multiple years. However, once symptoms appear the disease progresses rapidly, leading to widespread brain damage. Neurodegenerative symptoms can include dementia, ataxia (dysfunction of balance and coordination), convulsions and behavioural or personality changes. Death typically occurs within one to three years from the onset of clinical symptoms.
Currently, all known prion diseases are untreatable and fatal. Attempts to generate vaccines and pharmacological treatments are ongoing around the world. In livestock, elimination of the prion gene through genetic engineering has been shown to render animals immune to prion infection.