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.
Kretzschmar
H A
HA
Institut für Neuropathologic, Universität Gottingen, Federal Republic of Germany.
Giese
A
A
Brown
D R
DR
Herms
J
J
Keller
B
B
Schmidt
B
B
Groschup
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D016923:Cell Death; D002531:Cerebellum / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009498:Neurotoxins; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity; D017096:Prion Diseases / Q000473:pathology* / Q000503:physiopathology; D011328:Prions / Q000235:genetics / Q000633:toxicity; D012160:Retina / Q000473:pathology; D013569:Synapses / Q000502:physiology
D009498:Neurotoxins; D010446:Peptide Fragments; D011328:Prions