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Mitochondrial Uncoupling as a Therapeutic Target Following Neuronal Injury

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Abstract

Mitochondrial dysfunction is a prominent feature of excitotoxic insult and mitochondria are known to play a pivotal role in neuronal cell survival and death following injury. Following neuronal injury there is a well-documented increase in cytosolic Ca2+, reactive oxygen species (ROS) production and oxidative damage. In vitro studies have demonstrated these events are dependent on mitochondrial Ca2+ cycling and that a reduction in membrane potential is sufficient to reduce excitotoxic cell death. This concept has gained additional support from experiments demonstrating that the overexpression of endogenous mitochondrial uncoupling proteins (UCP), which decrease the mitochondrial membrane potential, decreases cell death following oxidative stress. Our group has demonstrated that upregulation of UCP activity can reduce excitotoxic-mediated ROS production and cell death whereas a reduction in UCP levels increases susceptibility to neuronal injury. These findings raise the possibility that mitochondrial uncoupling could be a potential novel treatment for acute CNS injuries.

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Authors and Affiliations

  1. Spinal Cord and Brain Injury Research Center and Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky

    P. G. Sullivan, Joe E. Springer, Edward D. Hall & Stephen W. Scheff

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  1. P. G. Sullivan
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Sullivan, P.G., Springer, J.E., Hall, E.D. et al. Mitochondrial Uncoupling as a Therapeutic Target Following Neuronal Injury. J Bioenerg Biomembr 36, 353–356 (2004). https://doi.org/10.1023/B:JOBB.0000041767.30992.19

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  • DOI: https://doi.org/10.1023/B:JOBB.0000041767.30992.19

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