ArticleCell death & disease2024
FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Protective role of irisin on bone in osteoporosis: a systematic review of rodent studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Pooled it
- Post-Translational Modifications in Traumatic Brain Injury: Decoding the Proteomic Landscape and Molecular Mechanisms of Secondary Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- TREM2 Attenuates Microglial Pyroptosis in Sepsis-Associated Encephalopathy Through Modulation of the mtDNA-cGAS-STING Pathway.Molecular neurobiology · 2026Article
- Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Arbutin mediated neuroprotection in zebrafish model of traumatic brain injury via modulating Nrf2/NF-κB pathway.Inflammopharmacology · 2026Article
- A zinc-coordinated cascade-responsive therapeutic nanoassembly for remodeling the pathological microenvironment and restoring mitochondrial homeostasis in spinal cord injury.Journal of nanobiotechnology · 2026Article
- Irisin promotes selective changes in hippocampal mitochondrial metabolism in mice.Biochemistry and biophysics reports · 2026Article
- Effect of Physical Exercise on Acute Post-traumatic Hyperexcitability: The Role of Thrombin/PAR1 Signaling.Molecular neurobiology · 2026Article
- Involvement of the PINK1/PARKIN pathway in enhancing mitochondrial function and mitophagy in reserpine-induced fibromyalgia mice through strength exercise and coenzyme Q10.European journal of applied physiology · 2026Article
- FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity.Journal of translational medicine · 2026Article
- Comprehensive Proteomic Profiling Reveals Dysregulation of Angiogenesis and Inflammatory Pathways in the Brains of SIRT3 Knockout Mice.Brain sciences · 2026Article
- Exercise-Induced Irisin: A Novel Strategy for Neuroinflammation Alleviation and Neurorepair in Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Irisin may be involved in exendin-4 mitochondrial action in human adipocytes.Archives of medical science : AMS · 2026Article
- Therapeutic Potential of Irisin in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Exercise-Induced FNDC5/Irisin Ameliorates Cognitive Impairment in Aged Mice, Associated with Antioxidant and Neurotrophic Responses.Antioxidants (Basel, Switzerland) · 2025Article
- FGF21 maintains redox homeostasis and promotes neuronal survival after traumatic brain injury by targeting SLC25A39-mediated mitochondrial GSH transport.Journal of translational medicine · 2025Article
- SIRT3 mediates CPT2 delactylation to enhance mitochondrial function and proliferation in goat granulosa cells.Journal of animal science and biotechnology · 2025Article
- Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases.Expert reviews in molecular medicine · 2025Review
- Irisin Regulates Microglia M1/M2 Polarization and Promotes Autophagy Through the Sirt3 Pathway to Alleviate POCD.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.
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