GENERAL-ASPECTS OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES AND HYPOTHESES ABOUT THE AGENTS

This article reviews the shared characteristics of the group of transm issible spongiform encephalopathies (SEs), both human and animal, and the major theories regarding the nature of the agents involved. All tr ansmissible SE diseases share two striking characteristics: the degene rative changes including vacuolation in the central nervous system, an d the assumption that these disorders are caused by unconventional, tr ansmissible agents. This article examines the major hypotheses that ha ve been postulated about these agents: the virus theory, the virino th eory, the prion theory, and the recently proposed 'unified theory'. Bo th the virus and the virino hypotheses assume that a small nucleic aci d is involved as part of the agent, while the prion hypothesis does no t. The prion model obviates the need for a role of a nucleic acid in t he propagation and replication of the agent, but does not explain the existence of strain variation. Nucleic acids in a micro-organism, as p roposed in the virino and the virus hypotheses, could explain this var iation. However, to date, no disease-specific nucleic acids have been identified. The 'unified' theory tries to reconcile the essentials of the virino and prion theories. The article also describes the discover y of the so-called prion protein (PrP), its isoforms, and the coding h ost gene, the PrP gene. It goes on to discuss the results of experimen ts with transgenic animals, indicating that mutations in the PrP gene may play a decisive role in the pathogenesis of at least some SEs. Fin ally, two different models, both involving the conversion of normal Pr P(C) into PrP(Sc) as part of the pathogenesis of SE, are discussed.