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Article Dans Une Revue Current Pharmaceutical Design Année : 2006

Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion.

S. Nicolas
  • Fonction : Auteur

Résumé

Evidence obtained over the past two decades shows that reactive oxygen species (ROS) are involved in brain lesions, including those due to cerebral ischemia-reperfusion. The mitochondria are the primary intracellular source of ROS, as they generate huge numbers of oxidative-reduction reactions and use massive amounts of oxygen. When anoxia is followed promptly by reperfusion, the resulting increase in oxygen supply leads to overproduction of ROS. In ischemic tissues, numerous studies have established a direct role for ROS in oxidative damage to lipids, proteins, and nucleic acids. Thus, mitochondria are both the initiator and the first target of oxidative stress. Mitochondrial damage can lead to cell death, given the role for mitochondria in energy metabolism and calcium homeostasis, as well as the ability of mitochondria to release pro-apoptotic factors such as cytochrome C and apoptosis-inducing factor (AIF). This review discusses possible mitochondrion-targeted strategies for preventing ROS-induced injury during reperfusion. The sequence of events that follow oxidative damage provides the outline for the review: thus, we will discuss protection of oxidative phosphorylation, mitochondrial membrane integrity and fluidity, and antioxidant or mild-uncoupling strategies for diminishing ROS production. Among mechanisms of action, we will describe the modulation of mitochondrial permeability transition pore (MPTP) opening, which may not only operate as a physiological Ca(2+) release mechanism, but also contribute to mitochondrial deenergization, release of pro-apoptotic proteins, and protection by ischemic preconditioning (IPC). Finally, we will review genetic strategies for controlling apoptotic protein expression, stimulating mitochondrial oxidative defences, and increasing mitochondrial proliferation.

Domaines

Neurobiologie
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Dates et versions

hal-00109788 , version 1 (25-10-2006)

Identifiants

  • HAL Id : hal-00109788 , version 1
  • PUBMED : 16472163

Citer

Céline Morin, S. Nicolas. Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion.. Current Pharmaceutical Design, 2006, 12 (6), pp.739-757. ⟨hal-00109788⟩

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