ArticleMolecular psychiatry2012
Regulation of the phosphatase calcineurin by insulin-like growth factor I unveils a key role of astrocytes in Alzheimer's pathology.
Article in Molecular psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Association between oxidative stress-related IGF-1 and prognosis after ischemic stroke: a systematic review and meta-analysis.Frontiers in neurology · 2025Pooled it
- Insulin-like growth factor 1 associated research in Alzheimer's disease: an exploratory trends analysis.Frontiers in neurologyPooled it
- Targeting Reactive Astrocytes with Flavonoids to Alleviate Neuroinflammation and Promote Synaptic Function.Molecular neurobiology · 2026Review
- Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis.Molecular neurobiology · 2025Article
- Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting.Inflammopharmacology · 2025Review
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Dexmedetomidine Pretreatment of Neuronal Cells Has Protective Effect Against Cell Death During Oxygen-glucose Deprivation/Reoxygenation, Based on IGF-1 Production.Juntendo Iji zasshi = Juntendo medical journal · 2024Article
- Causal relationship between circulating insulin-like growth factor-1 and Parkinson's disease: a two-sample Mendelian randomization study.Frontiers in aging neuroscience · 2024Article
- The Role of Insulin-like Growth Factor I in Mechanisms of Resilience and Vulnerability to Sporadic Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Calcineurin Signalling in Astrocytes: From Pathology to Physiology and Control of Neuronal Functions.Neurochemical research · 2023Review
- Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell-type lipidomics.Annals of the New York Academy of Sciences · 2022Review
- Insulin-like growth factor I sensitization rejuvenates sleep patterns in old mice.GeroScience · 2022Article
- Insulin regulates neurovascular coupling through astrocytes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Glial and myeloid heterogeneity in the brain tumour microenvironment.Nature reviews. Cancer · 2021Review
- Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.Ageing research reviews · 2021Review
- Circulating Insulin-Like Growth Factor I is Involved in the Effect of High Fat Diet on Peripheral Amyloid β Clearance.International journal of molecular sciences · 2020Article
- The Role of Astrocytes in CNS Inflammation.Trends in immunology · 2020Review
- Calcineurin Controls Expression of EAAT1/GLAST in Mouse and Human Cultured Astrocytes through Dynamic Regulation of Protein Synthesis and Degradation.International journal of molecular sciences · 2020Article
- Calcineurin-Mediated Hippocampal Inflammatory Alterations in Streptozotocin-Induced Model of Dementia.Molecular neurobiology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whether insulin-like growth factor I (IGF-I) signaling in Alzheimer's disease (AD) is beneficial or detrimental remains controversial. We now show that a competitive regulation by IGF-I of the phosphatase calcineurin in reactive, but not in quiescent astrocytes drives Alzheimer's pathology. Calcineurin de-phosphorylates the transcription factor Foxo3 in response to tumor necrosis factor-α (TNFα), an inflammatory cytokine increased in AD, activating nuclear factor-κB (NFκB) inflammatory signaling in astrocytes. In turn, IGF-I inactivates and displaces Foxo3 from calcineurin in TNFα-stimulated astrocytes by recruiting the transcription factor peroxisome proliferator-activated receptor-γ, and NFκB signaling is inhibited. This antagonistic mechanism reversibly drives the course of the disease in AD mice, even at advanced stages. As hallmarks of this calcineurin/Foxo3/NFκB pathway are present in human AD brains, treatment with IGF-I may be beneficial by antagonizing it.
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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.