Cell death in prion disease
Prion diseases are neurodegenerative transmissible diseases. The infectious agent, termed prion, is thought to consist of an altered host-encoded protein. The pathogenesis of these diseases which typically in a very short time lead to rampant nerve cell death and astrocytic gliosis is poorly understood. Investigations using the in situ endlabeling technique and electron microscopy in a scrapie model in the mouse (79A strain) show that nerve cell death is due to apoptosis. A cell culture model using a synthetic peptide of the prion protein (PrP106–126) shows that this peptide is toxic only to normal neurons whereas nerve cells derived from PrP knock-out (PrP0/0) mice are unaffected by this neurotoxic effect. In addition, microglia play a crucial part in this process by secreting reactive oxygen species. Experiments in animals will have to show whether these cell culture findings adequately reflect the in vivo pathogenesis.
KeywordsPurkinje Cell Xanthine Oxidase Prion Protein Prion Disease Bovine Spongiform Encephalopathy
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