The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury

Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxida...

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Bibliographic Details
Published in:Translational neuroscience 2015-01, Vol.6 (1), p.179-186
Main Authors: Normoyle, Kieran P., Kim, Miri, Farahvar, Arash, Llano, Daniel, Jackson, Kevin, Wang, Huan
Format: Article
Language:English
Subjects:
Adenosine triphosphate
ATP
Brain
Calcium
Cell death
Head injuries
Health services
Heterogeneity
Ischemia
Membrane potential
Mitochondria
Mitochondrial uncoupling protein 2
Neuronal cell death
Neuronal injury
Neuroprotection
Oxidative phosphorylation
Oxidative stress
Phosphorylation
Proteins
Review
Toxicity
Traumatic brain injury
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Summary:Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus reduce the mitochondrial membrane potential by dissipating the proton motive force. This uncoupling of oxidative phosphorylation from adenosine triphosphate (ATP) synthesis is potentially critical for protection against cellular injury as a result of TBI and stroke. A greater understanding of the underlying mechanism or mechanisms by which uncoupling protein-2 (UCP2) functions to maintain or optimize mitochondrial function, and the conditions which precipitate the failure of these mechanisms, would inform future research and treatment strategies. We posit that UCP2-mediated function underlies the physiological response to neuronal stress associated with traumatic and ischemic injury and that clinical development of UCP2-targeted treatment would significantly impact these patient populations. With a focus on clinical relevance in TBI, we synthesize current knowledge concerning UCP2 and its potential neuroprotective role and apply this body of knowledge to current and potential treatment modalities.
ISSN:2081-3856
2081-6936
2081-6936
DOI:10.1515/tnsci-2015-0019