Transmissible spongiform encephalopathies or prion diseases are chronic neurologic disorders characterized by long incubation periods, progressive noninflammatory disease of brain and spinal cord, a failure of a specific immune response, and a uniformly fatal course. They are transmissible within their natural species and to a limited extent across species barriers. The pathology is characterized by neuronal loss, gliosis, and vacuoles in cytoplasm of neural cells giving the spongiform appearance on microscopic examination. Infectivity copurifies with an isoform of a normal surface glycoprotein expressed primarily in the central nervous system. The function of the normal prion protein is unclear; but the misfolded protein – the prion – induces post-translational conversion of normal prion protein with a helical structure into the infectious isoform rich in β-pleated sheets. This abnormal protease-resistant protein accumulates in brain, leading to disease. To date nucleic acid has not been detected in the transmissible protein fraction. Prion diseases are recognized in animals (scrapie of sheep, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk) and humans (kuru, Creutzfeldt–Jakob disease [CJD], and the variant of CJD related to bovine spongiform encephalopathy). The human forms of disease can be divided into three groups: (1) sporadic CJD, which represents 85% to 90% of cases, (2) familial CJD due to mutations in the gene coding for prion protein, making up 10% of cases, and (3) transmitted CJD due to iatrogenic transmission, cannibalism in the case of kuru, and, recently, transmission of bovine spongiform encephalopathy to humans.
ASJC Scopus subject areas