Cited by 36Traumatic Brain Injury and Neurovascular DisturbancesMitochondrial Function and PathologyTraumatic Brain Injury Research

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

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Normoyle, Kieran P., Kim, Miri, Farahvar, Arash, Llano, Daniel, Jackson, Kevin, Wang, Huan·2015·Translational Neuroscience

Abstract

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.

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  1. [66]Qi L Cui X Dong W Barrera R Nicastro J Coppa GF Ghrelin attenuates brain injury after traumatic brain injury and uncontrolled hemorrhagic shock in rats Mol Med 2012 18 186 193 22160303 PMC3320141

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Authors
Normoyle, K. P., Kim, M., Farahvar, A., Llano, D., Jackson, K., & Wang, H.
Affiliations
  • University of Illinois Urbana-Champaign (US)
  • Carle Foundation Hospital (US)
Corresponding author
Wang, Huan
Venue
Translational Neuroscience
Published
2015-01-01
Volume
6
Issue
1
Pages
179-186
ISSN
  • 2081-3856 (ISSN-L)
  • 2081-6936
OpenAlex
W1532917355
Cited by
36
References
113
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 1
FWCI
2.35
Type
journal article
Language
en
Open access
Locations
  • Translational Neuroscience (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
UCP2, traumatic brain injury, neuroprotection, mitochondrial dysfunction, mitochondrial membrane potential, proton leak, oxidative stress, glutamate excitotoxicity, calcium toxicity, neuronal cell death, ischemic injury, stroke

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