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Translational Neuroscience

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

Kieran P. Normoyle
  • Department of Molecular and Integrative Physiology, University of Illinois at Urbana- Champaign, Urbana, IL, USA
  • College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • Department of Child Neurology, Massachusetts General Hospital, Boston, MA, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Miri Kim
  • College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Arash Farahvar / Daniel Llano
  • Department of Molecular and Integrative Physiology, University of Illinois at Urbana- Champaign, Urbana, IL, USA
  • Department of Neurology, Carle Foundation Hospital, Urbana, IL, USA
  • The Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kevin Jackson
  • The Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • Thermal Neuroscience Laboratory (TNL), Beckman Institute, University of Illinois at Urbana- Champaign, Urbana, IL, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Huan Wang
  • Department of Neurology, Carle Foundation Hospital, Urbana, IL, USA
  • Thermal Neuroscience Laboratory (TNL), Beckman Institute, University of Illinois at Urbana- Champaign, Urbana, IL, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-09-07 | DOI: https://doi.org/10.1515/tnsci-2015-0019


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.

Keywords: Neuronal injury; Mitochondria; Traumatic brain injury; Ischemia; Neuronal cell death


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About the article

Received: 2015-06-29

Accepted: 2015-07-20

Published Online: 2015-09-07

Citation Information: Translational Neuroscience, Volume 6, Issue 1, ISSN (Online) 2081-6936, DOI: https://doi.org/10.1515/tnsci-2015-0019.

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©2015 Kieran P. Normoyle et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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Yunhu Bai, Yang Bai, Shengming Wang, Feifei Wu, Dong Hui Wang, Jing Chen, Jing Huang, Hui Li, Yunqing Li, Shengxi Wu, Yayun Wang, and Yanling Yang
Free Radical Biology and Medicine, 2018
Dasfne Lee-Liu, Liangliang Sun, Norman J. Dovichi, and Juan Larraín
Molecular & Cellular Proteomics, 2018, Volume 17, Number 4, Page 592
Wei Hu, Xing-Bo Dang, Gang Wang, Shuai Li, and Yue-Lin Zhang
Neurochemistry International, 2018
Giorgia Pierelli, Rosita Stanzione, Maurizio Forte, Serena Migliarino, Marika Perelli, Massimo Volpe, and Speranza Rubattu
Oxidative Medicine and Cellular Longevity, 2017, Volume 2017, Page 1
Duraisamy Kempuraj, Ramasamy Thangavel, Govindhasamy P. Selvakumar, Smita Zaheer, Mohammad E. Ahmed, Sudhanshu P. Raikwar, Haris Zahoor, Daniyal Saeed, Prashant A. Natteru, Shankar Iyer, and Asgar Zaheer
Frontiers in Cellular Neuroscience, 2017, Volume 11
Speranza Rubattu, Rosita Stanzione, Franca Bianchi, Maria Cotugno, Maurizio Forte, Floriana Della Ragione, Salvatore Fioriniello, Maurizio D'Esposito, Simona Marchitti, Michele Madonna, Simona Baima, Giorgio Morelli, Sebastiano Sciarretta, Luigi Sironi, Paolo Gelosa, and Massimo Volpe
Cell Death and Disease, 2017, Volume 8, Number 6, Page e2891
Edward James Walter, Sameer Hanna-Jumma, Mike Carraretto, and Lui Forni
Critical Care, 2016, Volume 20, Number 1

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