Article

Activation of the amyloid cascade by intracerebroventricular injection of the protease inhibitor phosphoramidon.

Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Neurodegenerative Diseases (impact factor: 3.06). 02/2008; 5(3-4):166-9. DOI:10.1159/000113692 pp.166-9
Source: PubMed

ABSTRACT 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.

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Keywords

amyloid cascade
 
brain Abeta levels
 
brain beta-amyloid
 
distinct hippocampal neurons
 
findings reproduce pathological effects
 
intracerebroventricular injection
 
pathological effects
 
protease inhibitor phosphoramidon