ArticleThe Journal of biological chemistry2010
Oral administration of a GSK3 inhibitor increases brain insulin-like growth factor I levels.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016Pooled it
- Pooled it
- 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
- Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain.PNAS nexus · 2024Article
- Synthesis and Antimicrobial Activity of 3-Alkylidene-2-Indolone Derivatives.Molecules (Basel, Switzerland) · 2024Article
- Insulin-like growth factor binding protein-2 in at-risk adults and autopsy-confirmed Alzheimer brains.Brain : a journal of neurology · 2024Article
- Therapeutic Targeting of the GSK3β-CUGBP1 Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2023Article
- Sulfur-containing therapeutics in the treatment of Alzheimer's disease.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Article
- Targeting the Choroid Plexuses for Protein Drug Delivery.Pharmaceutics · 2020Review
- Drug Repurposing in Dentistry; towards Application of Small Molecules in Dentin Repair.International journal of molecular sciences · 2020Article
- Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.Brain communications · 2020Article
- Selective Ablation of Megalin in the Retinal Pigment Epithelium Results in Megaophthalmos, Macromelanosome Formation and Severe Retina Degeneration.Investigative ophthalmology & visual science · 2019Article
- The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor-Binding Proteins in the Nervous System.Biochemistry insights · 2019Review
- Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22.Nature cell biology · 2016Article
- Central IGF-I Receptors in the Brain are Instrumental to Neuroprotection by Systemically Injected IGF-I in a Rat Model for Ischemic Stroke.CNS neuroscience & therapeutics · 2016Article
- Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight.Scientific reports · 2016Article
- Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function.Stem cells international · 2016Review
- Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments.Neuropharmacology · 2012Review
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
Reduced brain input of serum insulin-like growth factor I (IGF-I), a potent neurotrophic peptide, may be associated with neurodegenerative processes. Thus, analysis of the mechanisms involved in passage of blood-borne IGF-I into the brain may shed light onto pathological mechanisms in neurodegeneration and provide new drug targets. A site of entrance of serum IGF-I into the brain is the choroid plexus. The transport mechanism for IGF-I in this specialized epithelium involves the IGF-I receptor and the membrane multicargo transporter megalin/LRP2. We have now analyzed this process in greater detail and found that the IGF-I receptor interacts with the transmembrane region of megalin, whereas the perimembrane domain of megalin is required for IGF-I internalization. Furthermore, a GSK3 site within the Src homology 3 domain of the C-terminal region of megalin is a key regulator of IGF-I transport. Thus, inhibition of GSK3 markedly increased internalization of IGF-I, whereas mutation of this GSK3 site abrogated this increase. Notably, oral administration of a GSK3 inhibitor to adult wild-type mice or to amyloid precursor protein/presenilin 1 mice modeling Alzheimer amyloidosis significantly increased brain IGF-I content. These results indicate that pharmacological modulation of IGF-I transport by megalin may be used to increase brain availability of serum IGF-I. Interestingly, GSK3 inhibitors such as those under development to treat Alzheimer disease may show therapeutic efficacy in part by increasing brain IGF-I levels, an effect already reported for other neuroprotective compounds.
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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.