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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2015-09-01
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doaj-art-e8becf2a20524e469e9f27a0a84d15d42018-09-02T04:42:25ZengDe GruyterTranslational Neuroscience2081-69362015-09-016110.1515/tnsci-2015-0019tnsci-2015-0019The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injuryNormoyle Kieran P.0Kim Miri1Farahvar Arash2Llano Daniel3Jackson Kevin4Wang Huan5Department of Molecular and Integrative Physiology, University of Illinois at Urbana- Champaign, Urbana, IL, USACollege of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USADepartment of Neurosurgery, Carle Foundation Hospital, Urbana, IL, USADepartment of Molecular and Integrative Physiology, University of Illinois at Urbana- Champaign, Urbana, IL, USAThe Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USADepartment of Neurology, Carle Foundation Hospital, Urbana, IL, USATraumatic 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.http://www.degruyter.com/view/j/tnsci.2015.6.issue-1/tnsci-2015-0019/tnsci-2015-0019.xml?format=INTNeuronal injury Mitochondria Traumatic brain injury Ischemia Neuronal cell death |
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author |
Normoyle Kieran P. Kim Miri Farahvar Arash Llano Daniel Jackson Kevin Wang Huan |
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Normoyle Kieran P. Kim Miri Farahvar Arash Llano Daniel Jackson Kevin Wang Huan The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury Translational Neuroscience Neuronal injury Mitochondria Traumatic brain injury Ischemia Neuronal cell death |
author_facet |
Normoyle Kieran P. Kim Miri Farahvar Arash Llano Daniel Jackson Kevin Wang Huan |
author_sort |
Normoyle Kieran P. |
title |
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
title_short |
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
title_full |
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
title_fullStr |
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
title_full_unstemmed |
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
title_sort |
emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury |
publisher |
De Gruyter |
series |
Translational Neuroscience |
issn |
2081-6936 |
publishDate |
2015-09-01 |
description |
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. |
topic |
Neuronal injury Mitochondria Traumatic brain injury Ischemia Neuronal cell death |
url |
http://www.degruyter.com/view/j/tnsci.2015.6.issue-1/tnsci-2015-0019/tnsci-2015-0019.xml?format=INT |
_version_ |
1612657301095710720 |