Past and Future of Diagnosis and Therapy of Transmissible Spongiform Encephalopathy

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, including Creutzfeldt-Jakob disease (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, represent diseases with complex and still poorly understood molecular mechanisms (Prusiner, 1998).The protein-only hypothesis postulates a possible pathogenic mechanism involving the prion protein.The helix rich normal prion protein (PrPC) is found to be infected by its -sheet rich abnormal proteinase K (PK)-resistant form, PrPSc, and is converted into PrPSc (Prusiner, 1998).This infection will lead to the aggregation of PrPSc-based amyloid fibrils that accumulate in the peripheral and invade to the central nervous system and damage neurons.In this chapter, we discuss current understanding of pathogenic mechanisms in this priononly hypothesis based disease in Section 2. This understanding then leads to the discussions of the past and present developments in both diagnosis and therapy for these diseases in Section 3. Based on the understanding of pathogenic mechanisms and current diagnosis and therapeutic strategies, we propose an alternative strategy.The proposal considers an aptamer-based theranostic approach to detect and prevent the aggregation of amyloid plaques in Section 4. Note that aptamer is defined as short nucleic acid sequences, and designed through Systematic Evolution of Ligands by EXponential enrichment (SELEX) (James, 2000).It is hoped that this proposal will open a novel research direction and eventually lead to a better diagnosis and treatment of prion diseases in the future. The infectivity of prion diseasesNumerous models have been developed to provide better understanding of the pathogenesis of the prion diseases.One of models advanced is the template-assistance model (Prusiner, 1998; Horiuchi & Caughy, 1999;Tompa et al., 2002).This model assumed that PrPC, which is normally more stable than PrPSc in isolation, would in the presence of PrPSc convert to the latter via a transient catalytic interaction with it.The implication is that a dimer of PrPSc's is energetically more stable than a system of non-interacting PrPC and PrPSc.This was supported by Morrissey and Shakhnovich's computational analyses (Morrissey & Shakhnovich, 1999).When there are other PrPSc's present, the initial www.intechopen.com

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