Activation of the amyloid cascade by intracerebroventricular injection of the protease inhibitor phosphoramidon.
We presently investigated the pathological effects of prolonged inhibition of brain beta-amyloid (Abeta) degradation in vivo. The results obtained revealed that intracerebroventricular injection of the protease inhibitor phosphoramidon into wild-type mice for up to a month elevated the soluble and deposited brain Abeta levels and concomitantly induced the neurodegeneration of distinct hippocampal neurons as well as neuroinflammation. These findings reproduce pathological effects associated with the initial stages of the amyloid cascade and provide a novel model system for studying their underlying mechanisms.
Nisemblat
Yotam
Y
Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Belinson
Haim
H
Dolev
Iftach
I
Michaelson
Daniel M
DM
D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006020:Glycopeptides / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000682:Amyloid; D006020:Glycopeptides; D011480:Protease Inhibitors; C008890:phosphoramidon