Molecular Basis of Prion Diseases

Publisher Summary The prion diseases are a related group of neurode­generative conditions that affect both humans and animals. The demonstration of transmission of prion disease by inoc­ulation of scrapie brain isolates into sheep, and of kuru, CJD and GSS brain isolates into primates, formed the basis for the concept of “transmissible dementias.” Human prion diseases encompass the three etiological types of prion disease including inherited, sporadic and acquired forms. Approximately, 15% of the human prion diseases are associ­ated with autosomal dominant pathogenic mutations in PRNP gene. Human prion diseases are associated with a range of clini­cal presentations and are classified by both clinicopathologi­cal syndrome and etiology, with subclassification according to the molecular criteria. All forms are invariably fatal following clinical onset; however, there is marked phenotypic variabil­ity depending upon etiology. Although the pathological consequences of prion infection occur in the central nervous system and experimental trans­mission of these diseases are most efficiently accomplished by intracerebral inoculation, most natural infections do not occur by these means.