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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Main Authors:	Normoyle Kieran P., Kim Miri, Farahvar Arash, Llano Daniel, Jackson Kevin, Wang Huan
Format:	Article
Language:	English
Published:	De Gruyter 2015-09-01
Series:	Translational Neuroscience
Subjects:	Neuronal injury Mitochondria Traumatic brain injury Ischemia Neuronal cell death
Online Access:	http://www.degruyter.com/view/j/tnsci.2015.6.issue-1/tnsci-2015-0019/tnsci-2015-0019.xml?format=INT

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spelling	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
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	Normoyle Kieran P. Kim Miri Farahvar Arash Llano Daniel Jackson Kevin Wang Huan
spellingShingle	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

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

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