Prion-mediated disease

The potential for preventing infectious disease is far from complete, and there is a continuing need for worthwhile research programs. Current challenges include HIV and prion-mediated disease,... 

Polyene antibiotics can be also used to enhance several-fold the efficiency of DNA-mediated gene transfer in mammalian cells (24), to inhibit the replication of HIV (25), or to delay the incubation period of a putative prion-caused disease of man (Creutifeldt-Jakob disease) and animals. At the moment, no therapy is available for the cure of these fata central nervous system diseases (26). 

One such application of RSEs, or their constituent bond dissociation energies, is in the study of radical-mediated degradation mechanisms. For example, based on an examination of the relevant C-H and S-H bond dissociation energies in model peptides. Rank et al. postulated a mechanism for generating and propagating oxidative damage via a Met residue of the Ap peptide of Alzheimer s disease or the prion peptide of Creutzfeldt-Jakob disease. In a similar manner, Li et al. used C-H BDE calculations to identify the most vulnerable sites for radical-mediated damage in... 

Immune cell trafficking into the CNS is important in mediating neuroimmune diseases. Immune cell invasion is an early event in multiple sclerosis and EAE (Wolburg et al., 2005). Infected immune cells are a mechanism by which HTV-l (Koyanagi et al., 1997 Nottet et al., 1996) and perhaps prions (Klein et al., 1997) invade the CNS. 

Like other neurodegenerative disorders, such as Alzheimer s and Parkinson s disease, prion diseases are characterized by the formation and accumulation of an aberrantly folded protein in the brain. However, a unique feature of prion diseases is their transmissibility. Prions (acronym for proteinaceous infectious particles) are mainly composed of PrPSc, polysaccharides, and lipids, but lack nucleic acids longer than 25 nucleotides, arguing against an essential role for DNA/RNA in mediating infectivity [35, 36]. Indeed, recent experiments support the protein-only hypothesis recombinant PrP expressed in and purified from bacteria and subsequently misfolded in vitro can transmit the disease [37-40]. 

In addition, Af) oligomers bind to PrP with nanomolar affinity (Lauren et al., 2009). Anti-PrP - antibodies inhibit Afioligomer binding to PrP - and rescue synaptic plasticity in hippocampal slices from oligomeric A toxicity. Based on these results, it is proposed that PrP - mediates AP-oligomer-induced synaptic dysfunction. These results also support the view that there are mechanistic similarities between AD and prion disease (CJD) (Fig. 8.3) (Lauren et al., 2009 Nygaard and Strittmatter, 2009 Gunther and Strittmater, 2010). 

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