The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury
Open accessAbstract
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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The beneficial effect of UCP2 was also observed in traumatic brain injury or neurodegenerative conditions.
“This beneficial effect of UCP2 was also observed in traumatic brain injury [292] or neurodegenerative conditions [293].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [292]
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Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
Sorted by citations
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“This beneficial effect of UCP2 was also observed in traumatic brain injury [292] or neurodegenerative conditions [293].”
Background
- 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
- Publisher
- Walter de Gruyter GmbH
- Published
- 2015-01-01
- Volume
- 6
- Issue
- 1
- Pages
- 179-186
- ISSN
- 2081-3856 (ISSN-L)
- 2081-6936
- PMC
- PMC4936626
- 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
- gold
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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