ArticleMolecular neurobiology2015
Transthyretin Induces Insulin-like Growth Factor I Nuclear Translocation Regulating Its Levels in the Hippocampus.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Differential Expression and Alternative Splicing Pattern in Female and Male GroupsAnimals : an open access journal from MDPI · 2026Article
- Profibrotic Biomarkers Correlate with Clinical Presentation and Outcome in Cardiac Transthyretin Amyloidosis.International journal of molecular sciences · 2025Article
- Transthyretin, a novel prognostic marker of POCD revealed by time-series RNA-sequencing analysis.Molecular psychiatry · 2025Article
- Transthyretin as a therapeutic target: the future of disease-modifying therapies for Alzheimer's disease.Molecular biology reports · 2025Review
- Tetrameric Transthyretin as a Protective Factor Against Alzheimer's Disease.Molecular neurobiology · 2025Review
- Transthyretin Orchestrates Vitamin B12-Induced Stress Resilience.Biological psychiatry · 2025Article
- Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP.Brain : a journal of neurology · 2023Article
- Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs.eNeuro · 2023Article
- Salivary Proteomics Identifies Transthyretin as a Biomarker of Early Dementia Conversion.Journal of Alzheimer's disease reports · 2022Article
- The role of transthyretin in cell biology: impact on human pathophysiology.Cellular and molecular life sciences : CMLS · 2021Review
- Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes.Animals : an open access journal from MDPI · 2020Article
- Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.Brain communications · 2020Article
- Wilm's tumor 1 promotes memory flexibility.Nature communications · 2019Article
- Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy.Endocrine reviews · 2019Review
- Integrated Hypothalamic Transcriptome Profiling Reveals the Reproductive Roles of mRNAs and miRNAs in Sheep.Frontiers in genetics · 2019Article
- Neuron-derived transthyretin modulates astrocytic glycolysis in hormone-independent manner.Oncotarget · 2017Article
- Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia.Cell death and differentiation · 2016Article
- Transthyretin participates in beta-amyloid transport from the brain to the liver--involvement of the low-density lipoprotein receptor-related protein 1?Scientific reports · 2016Article
- Transthyretin Antisense Oligonucleotides Lower Circulating RBP4 Levels and Improve Insulin Sensitivity in Obese Mice.Diabetes · 2015Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transthyretin (TTR) is the carrier protein of thyroxine (T4) and binds to retinol-binding protein (RBP)-retinol complex. It is mainly synthesized by both liver and choroid plexuses of the brain. Besides these properties, it has a neuroprotective role in several contexts such as Alzheimer's disease (AD) and cerebral ischemia. Activation of insulin-like growth factor receptor I (IGF-IR) pathways and increased levels of TTR are associated with absence of neurodegeneration in an AD mouse model. In the present study, we verified that young/adult TTR null mice had decreased levels of IGF-IR in the hippocampus, but not in choroid plexus when compared with wild-type age-matched controls. Moreover, we could also demonstrate that conditional silencing of peripheral TTR did not have any influence in hippocampal IGF-IR levels, indicating that TTR effect on IGF-IR levels is due to TTR mainly synthesized in the choroid plexus. In vitro cellular studies, using NIH3T3 cell line and primary cultured hippocampal neurons, we showed that TTR upregulates IGF-IR at the transcription and translation levels and that is dependent on receptor internalization. Using a GFP-IGF-IR fusion protein, we also found that TTR triggers IGF-IR nuclear translocation in cultured neurons. We could also see an enrichment of IGF-IR in the nuclear fraction, after TTR stimulation in NIH3T3 cells, indicating that IGF-IR regulation, triggered by TTR is induced by nuclear translocation. In summary, the results provide evidence of a new role of TTR as a transcription inducer of IGF-IR in central nervous system (CNS), unveiling a new role in neuroprotection.
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