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...

Full description

Bibliographic Details
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:
Online Access:http://www.degruyter.com/view/j/tnsci.2015.6.issue-1/tnsci-2015-0019/tnsci-2015-0019.xml?format=INT
id doaj-art-e8becf2a20524e469e9f27a0a84d15d4
recordtype oai_dc
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