Prions: health scare and biological challenge

Abstract

Prions are the infectious agents that cause both bovine spongiform encephalopathy in cows and Creutzfeldt?Jakob disease in humans. In both, clinically detectable degeneration is only seen in the central nervous system (CNS). In yeast, prions are defined as proteins that can exist in two conformations, one of which can induce the conversion of further prion molecules from one conformation into the other, and so is self-perpetuating and heritable. In vitro conversion of the mammalian endogenous prion protein ? PrP^C ? results in a moiety that has the physiochemical properties of Prp^Sc, the disease-associated protein. No experiments have so far unambiguously shown that Prp^Sc is a transmissable agent. Neuronal cytotoxicity of Prp^Sc depends on the expression of cellular PrP^C by target cells. Evidence indicates that the conversion of PrP^C into PrP^Sc is the deleterious event. Prp^C can adopt two orientations in the membrane, one of which, ^CtmPrP, correlates well with neurodegenerative changes. Like viruses, prions can enter the enter the CNS through the immune system, lymphocytes and follicular dendritic cells. The presence of PrP^C and terminally differentiated B cells is essential for invasion by infectious prions. How prions move from the germinal centres to the CNS is less clear, but might involve peripheral nerves and lymphocytes. New variant (nv) CJD can be distinguished from sporadic CJD in that it mainly affects young people, develops more slowly and is distinguished by widespread vacuolation of the cortical neurophil and an accumulation of protein plaques in the brain. Studies of neural degeneration patterns in mice, the biochemical properties of prions and epidemiology support the idea that the agent causing nvCJD is identical to that causing BSE when transmitted to humans. It is unclear whether there is a subclinical or carrier status of the diease. To rule out the possibility of iatrogenic transmission, attention is now focused on preparation of blood products. Understanding the molecular basis of invasion should help to identify possible targets for intervention.