ArticleMolecular neurodegeneration2012
Frataxin deficiency unveils cell-context dependent actions of insulin-like growth factor I on neurons.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Quercetagetin Ameliorates Heat Stress-Induced Intestinal Damage via Oxidative Stress, Inflammation and Gut Microbiota in Mice.Microorganisms · 2026Article
- Astrocytic mitochondrial frataxin-A promising target for ischemic brain injury.CNS neuroscience & therapeutics · 2023Review
- Loss of filamentous actin, tight junction protein expression, and paracellular barrier integrity in frataxin-deficient human brain microvascular endothelial cells-implications for blood-brain barrier physiology in Friedreich's ataxia.Frontiers in molecular biosciences · 2023Article
- Neuroinflammation in Friedreich's Ataxia.International journal of molecular sciences · 2022Review
- Review
- Frataxin Deficit Leads to Reduced Dynamics of Growth Cones in Dorsal Root Ganglia Neurons of Friedreich's Ataxia YG8sR Model: A Multilinear Algebra Approach.Frontiers in molecular neuroscience · 2022Article
- Drug Repositioning in Friedreich Ataxia.Frontiers in neuroscience · 2022Review
- Cerebellar Astrocytes: Much More Than Passive Bystanders In Ataxia Pathophysiology.Journal of clinical medicine · 2020Review
- Insulin Peptides as Mediators of the Impact of Life Style in Alzheimer's disease.Brain plasticity (Amsterdam, Netherlands) · 2018Review
- Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.Cerebellum (London, England) · 2017Article
- Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich's ataxia patients.Scientific reports · 2017Article
- Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich's Ataxia Transgenic Mice.International journal of molecular sciences · 2016Article
- Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Astrocyte Resilience to Oxidative Stress Induced by Insulin-like Growth Factor I (IGF-I) Involves Preserved AKT (Protein Kinase B) Activity.The Journal of biological chemistry · 2016Article
- Article
- Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury.F1000Research · 2014Article
- IGF-1 in autosomal dominant cerebellar ataxia - open-label trial.Cerebellum & ataxias · 2014Article
- IGF-1 in Friedreich's Ataxia - proof-of-concept trial.Cerebellum & ataxias · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFriedreich's ataxia (FRDA) is a neurodegenerative disease caused by deficiency of the mitochondrial iron chaperone frataxin (Fxn). FRDA has no cure, but disease-modifying strategies to increase frataxin are under study. Because insulin-like growth factor I (IGF-I) has therapeutic effects in various types of cerebellar ataxia and exerts protective actions on mitochondrial function, we explored the potential Fxn-stimulating activity of this growth factor on brain cells.
resultsIGF-I normalized frataxin levels in frataxin-deficient neurons and astrocytes through its canonical Akt/mTOR signaling pathway. IGF-I also stimulated frataxin in normal astrocytes but not in normal neurons, whereas IGF-I stimulated the Akt/mTOR pathway in both types of cells. This cell context-dependent action of IGF-I on neurons suggested that the intrinsic regulation of Fxn in neurons is different than in astrocytes. Indeed, neurons express much higher levels of frataxin and are much more sensitive to Fxn deficiency than astrocytes; i.e.: only neurons die in the absence of frataxin. In addition, the half-life of frataxin is shorter in neurons than in astrocytes, while after blockade of the proteasome only neurons responded to IGF-I with an increase in frataxin levels. We also explore a potential therapeutic utility of IGF-I in FRDA-like transgenic mice (YG8R mice) and found that treatment with IGF-I normalized motor coordination in these moderately ataxic mice.
conclusionExposure to IGF-I unveiled a cell-specific regulation of frataxin in neurons as compared to astrocytes. Collectively, these results indicate that IGF-I exerts cell-context neuroprotection in frataxin deficiency that maybe therapeutically effective.
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