Prion Diseases

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rion diseases or transmissible spongiform encephalopathies (table 1) are characterised by the deposition of PrP Sc , an abnormal form of a normal cellular protein, PrP C .These diseases exist in sporadic (idiopathic), genetic, and acquired forms. PRION PROTEIN cThe normal prion protein, PrP C , is encoded by the prion gene (PRNP) on human chromosome 20, with equivalent prion genes in animals.The function of PrP C is not known but it may have roles in anti-oxidant systems and cellular copper metabolism.In prion diseases, the normal host gene produces the normal host PrP C but there is then an incompletely understood post-translational conformational change to a disease related form, PrP Sc .PrP Sc is relatively insoluble and relatively protease resistant, and accumulates in tissues forming amyloid structures.The precise pathogenesis of the neurological illness is not known, but PrP Sc deposition is associated with the neuropathological changes of neuronal loss, astrocytic gliosis, and spongiform change (fig 1).In the acquired prion diseases, material from an affected host infects another.The infective agent (termed the ''prion'') has not been fully characterised, but PrP Sc is associated with infectivity.Since the prion protein has such a central role, it is not surprising to find that the prion protein gene, PRNP, is also important (even in non-genetic forms of TSE).In human prion diseases, a common polymorphism at codon 129 has important effects on susceptibility to disease, the resulting clinical characteristics and the incubation period (in acquired forms).At codon 129 of PRNP, an individual may encode for methionine (M) or valine (V) and, therefore, all humans are MM or VV homozygotes or MV heterozygotes.In the normal UK population, the distributions are approximately: MM 40%, VV 10%, MV 50%.Some effects of this polymorphism are discussed in specific sections below.Two basic facts illustrate the potential importance of this polymorphism: approximately 80% of UK sporadic CJD cases and, to date, all cases of variant CJD, are MM (table 2).This review is concerned with those human prion diseases of relevance to clinical neurological practice in the UK: Creutzfeld-Jakob disease (CJD), Gerstmann-Stra ¨ussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).These diseases are very rare but, nonetheless, are of importance and interest.