ArticleActa neuropathologica communications2014
Astroglial PGC-1alpha increases mitochondrial antioxidant capacity and suppresses inflammation: implications for multiple sclerosis.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Metabolomics in Multiple Sclerosis: Advances, Challenges, and Clinical Perspectives-A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Overexpression of PGC-1α reduces inflammation and protects against focal cerebral ischaemia/reperfusion injury.Archives of medical science : AMS · 2026Article
- Microglial PGC-1α alleviates synaptic damage and cognitive impairments following anesthesia and surgery by suppressing excessive synaptic pruning in aged mice.International journal of biological sciences · 2026Article
- PGC-1α mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neuroinflammatory response via inhibiting microglial ferroptosis in ischemic stroke.Journal of translational medicine · 2025Article
- Astrocytes in maintaining neuronal health and brain function: interplay of aging, diet, and environment.Metabolic brain disease · 2025Review
- LCN2 Regulates Microglia Polarization Through the p38MAPK-PGC-1α-PPARγ Pathway to Alleviate Traumatic Brain Injury.Cell biochemistry and biophysics · 2025Article
- The Possible Role of Metformin and Fibroblast Growth Factor-21 in Multiple Sclerosis Neuropathology: Birds of a Feather Flock Together.The European journal of neuroscience · 2025Review
- Functional Recovery Promotion After Spinal Cord Injury With Astaxanthin Treatment in Preclinical Studies: A Systematic Review and Meta-Analysis.Neurology research international · 2025Review
- Review
- Orchestrating Stress Responses in Multiple Sclerosis: A Role for Astrocytic IFNγ Signaling.International journal of molecular sciences · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α in the Spotlight with Multiple Sclerosis.Neuroscience bulletin · 2024Article
- Aging promotes an increase in mitochondrial fragmentation in astrocytes.Frontiers in cellular neuroscience · 2024Article
- Natural Mitochondria Targeting Substances and Their Effect on Cellular Antioxidant System as a Potential Benefit in Mitochondrial Medicine for Prevention and Remediation of Mitochondrial Dysfunctions.Current issues in molecular biology · 2023Review
- Metformin induces M2 polarization via AMPK/PGC-1α/PPAR-γ pathway to improve peripheral nerve regeneration.American journal of translational research · 2023Article
- The Role of the Thioredoxin System in Brain Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis.Pharmaceutics · 2022Article
- Edaravone attenuates disease severity of experimental auto-immune encephalomyelitis and increases gene expression of Nrf2 and HO-1.Physiological research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence suggests that reactive oxygen species (ROS) produced by inflammatory cells drive axonal degeneration in active multiple sclerosis (MS) lesions by inducing mitochondrial dysfunction. Mitochondria are endowed with a variety of antioxidant enzymes, including peroxiredoxin-3 and thioredoxin-2, which are involved in limiting ROS-induced damage. In this study, we explored the distribution and role of the mitochondrial antioxidants peroxiredoxin-3 and thioredoxin-2 as well as their regulator peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC-1α) in MS pathogenesis. Immunohistochemical analysis of a large cohort of MS patients revealed a striking upregulation of PGC-1α and downstream mitochondrial antioxidants in active demyelinating MS lesions. Enhanced expression was predominantly observed in reactive astrocytes. To elucidate the functional role of astrocytic PGC-1α in MS pathology, we generated human primary astrocytes that genetically overexpressed PGC-1α. Upon an oxidative insult, these cells were shown to produce less ROS and were found to be more resistant to ROS-induced cell death compared to control cells. Intriguingly, also neuronal cells co-cultured with PGC-1α-overexpressing astrocytes were protected against an exogenous oxidative attack compared to neuronal cells co-cultured with control astrocytes. Finally, enhanced astrocytic PGC-1α levels markedly reduced the production and secretion of the pro-inflammatory mediators interleukin-6 and chemokine (C-C motif) ligand 2. Our findings suggest that increased astrocytic PGC-1α in active MS lesions might initially function as an endogenous protective mechanism to dampen oxidative damage and inflammation thereby reducing neurodegeneration. Activation of PGC-1α therefore represents a promising therapeutic strategy to improve mitochondrial function and repress inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.