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FP6

MITOCHONDRIA & ABETA Résumé de rapport

Project ID: 44907
Financé au titre de: FP6-MOBILITY
Pays: Lithuania

Final Activity and Management Report Summary - MITOCHONDRIA & ABETA (Mitochondria and beta-amyloid in brain ischemia/reperfusion)

Accumulation of beta-amyloid peptide is a key factor of Alzheimer's disease. Some authors suggested that ischemia/repefusion increases beta-amyloid production via mitochondria. beta-amyloid peptides are prone to aggregation, and it is recently found that oligomeric forms of those peptides are more toxic to neurons than others. Oestrogen treatment protects neurons against ischemia-induced damage and this action involves mitochondria. The study tested whether brain ischemia/reperfusion induces beta-amyloid production, how different size beta-amyloid peptides affect neuronal cell viability in culture and activity of isolated brain mitochondria, and how these effects are modulated by oestrogenic.

The study is performed on primary brain cell cultures and isolated brain mitochondria from rat. We found that ischemia-induced neuronal apoptosis and ischemia plus reperfusion-induced neuronal necrosis is prevented by beta-amyloid synthesis inhibitors 5 microM z-Leu-Leu-Nle-CHO and 50 microM pepstatin A methyl ester. Oligomers of beta-amyloid at submicromolar concentrations causes neuronal death that is prevented by 17beta-estradiol.

Respiration of brain mitochondria is inhibited in the presence of beta-amyloid oligomers, and this effect is partially reversed by added cytochrome c. Fibrillar and monomeric forms of beta-amyloid has no toxic effect on neurons or on isolated brain mitochondria. The results suggest that ischemia/reperfusion might induce beta-amyloid production and demonstrate that oligomeric beta-amyloid is the most toxic for neurons. Mitochondria are one of the mediators of this toxicity.

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