Chapter 17 - Ataxia in Prion Diseases

Abstract

Human transmissible spongiform encephalopathies (TSEs) or prion diseases represent a unique group of neuro-degenerative disorders that may be sporadic, infectious, or hereditary. Infectious forms of TSE may cause large out-breaks such as epidemics of kuru and variant Creutzfeldt-Jakob disease. Sporadic and hereditary forms of TSE are also found to be experimentally transmissible to non-human primates and rodents with similarly long incubation times. Recent advances in cellular and molecular biology have yielded increasingly strong evidence that TSE results from the accumulation in the brain of an abnormal isoform of prion protein, a post-translational modification of a normal host protein encoded by the PRNP gene. This abnormal isoform and its toxic fragments gradually accumulate in neurons resulting in neuronal death and other pathogenic effects that are responsible for the TSE phenotypes. Regular transmission of TSE to susceptible laboratory animals, including apes and monkeys, Syrian hamsters, and several strains of mice, is demonstrated in early TSE studies Also, transmission of kuru by cannibalistic rituals was experimentally confirmed by studies of alimentary transmission of TSE in Syrian hamsters by neuro-pathologic confirmation and establishing infectivity of their brain tissue.