NR ABTG
AU Brown,D.R.; Schmidt,B.; Kretzschmar,H.A.
TI Role of microglia and host prion protein in neurotoxicity of a prion protein fragment
QU Nature 1996 Mar 28; 380(6572): 345-7
PT journal article
AB The prion protein PrPc is a glycoprotein of unknown function normally found in neurons and glia. It is involved in diseases such as bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease. PrPsc, an altered isoform of PrPc that is associated with disease, shows greater protease resistance and is part of the infectious agent, the prion. Prion diseases are characterized by neuronal degeneration, gliosis and accumulation of PrPsc. Mice devoid of PrPc are resistant to scrapie. A fragment of human PrP consisting of amino acids 106-126 that forms fibrils in vitro is toxic to cultured neurons. Here we show that this toxic effect requires the presence of microglia which respond to PrP106-126 by increasing their oxygen radical production. The combined direct and microglia-mediated effects of PrP106-126 are toxic to normal neurons but are insufficient to destroy neurons from mice not expressing PrPc.
IN Den Aminosäuren 106-126 des menschlichen Prionproteins entsprechende synthetische Peptide wirkten auf normale Mausneuronen bei Konzentrationen von 20-80 µM nur in Anwesenheit von Mikrogliazellen aus der Maushirnrinde toxisch. Die Wirkung der Mikrogliazellen beruht offenbar auf der Abgabe von Sauerstoffradikalen, die aber nur auf Neuronen mit dem Prionprotein tödlich wirken. Astrozyten besitzen keine entsprechende Wirkung.
ZR 22 Zitate
MH Amino Acid Sequence; Animal; Cell Survival/drug effects; Cells, Cultured; Cerebellum/*drug effects/pathology; Coculture; Leucine/analogs & derivatives/pharmacology; Mice; Mice, Inbred C57BL; Microglia/drug effects/*physiology; Molecular Sequence Data; Neurotoxins/*toxicity; Oxidative Stress; Peptide Fragments/*toxicity; PrPc Proteins/biosynthesis; Prions/*toxicity; Support, Non-U.S. Gov't
AD Institut für Neuropathologie, Universität Göttingen, Germany.
SP englisch
PO England
OR Prion-Krankheiten 2