NR AGUX
AU Kretzschmar,H.A.; Giese,A.; Brown,D.R.; Herms,J.W.; Keller,B.; Schmidt,B.; Groschup,M.H.
TI Cell death in prion disease
QU Journal of Neural Transmission. Supplementum 1997; 50: 191-210
PT journal article; review; review, tutorial
AB 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.
ZR 72
MH Amino Acid Sequence; Animal; *Apoptosis; Astrocytes/drug effects/pathology; Brain/*pathology/physiopathology; *Cell Death; Cerebellum/pathology; Disease Models, Animal; Gliosis; Human; Mice; Mice, Knockout; Molecular Sequence Data; Neurons/drug effects/pathology/physiology; Neurotoxins; Peptide Fragments/chemistry/toxicity; Prion Diseases/*pathology/physiopathology; Prions/genetics/toxicity; Retina/pathology; Support, Non-U.S. Gov't; Synapses/physiology
AD Institut für Neuropathologie, Universität Göttingen, Federal Republic of Germany.
SP englisch
PO Österreich