FP6Реинтеграция2006–2007

MITOCHONDRIA & ABETA · Mitochondria and beta-amyloid in brain ischemia/reperfusion

6РП — Действия „Мария Кюри“

Период: 2006-11-17 → 2007-06-16
Финансиране от ЕС: 40 000 €
Участници: 1
Схема: ERG

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между исхемията на мозъка, работата на митохондриите и натрупването на бета-амилоидни протеини се анализира чрез опити с клетки от плъхове. Резултатите помагат да се разбере как определени форми на тези протеини увреждат невроните и как естрогенът може да ги защити.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

This project is to test whether beta-amyloid peptide accumulates in mitochondria during brain ischemia/reperfusion, whether it impairs mitochondrial functions and induces cell death in a mitochondrial permeability transition-dependent way, and whether estrogens and antioxidants can prevent these events. Accumulation of beta-amyloid peptide (Abeta is a key factor in Alzheimer's disease (AD). Increased levels of Abeta are observed in both ischemia/reperfusion- and AD-damaged brains, and ischemia often precedes AD.Mitochondria are the primary target of ischemia and subsequent reperfusion, and they are both the source and the target of reactive oxygen species (ROS) generated under hypoxic and reoxygenated conditions. Recent evidence indicates that Abeta accumulates intraneuronally and intramitochondrially. In mitochondria, Abeta is shown to inhibit cytochrome c oxidase, to change mitochondrial membrane properties, mitochondrial capacity to accumulate calcium, and to stimulate mitochondria-related apoptosis.

Оригинален текст от CORDIS (на английски).

Участници

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES · KAUNASКоординаторЛитва