ArticleMolecular psychiatry2017
Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03862950 (A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome), which is not on this map. Cited by 62 papers.
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.
A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS)
Who cites it
62 citing papers in PubMed, 95 citations in OpenAlex.
- Effects of Metformin on children with Fragile X Syndrome: a randomized, double-blind, placebo-controlled trial.Molecular autism · 2025Trial
- GABA as an Overlooked Mediator of Metformin Action: GABA-mediated Neuropsychiatric and Hepatoprotective Activities of Metformin.Annals of neurosciences · 2026Review
- Up-regulation of Minibrain/DYRK1A contributes to macrocephaly and brain overgrowth in aProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sleep in a mouse model of fragile X syndrome is resistant to metabolic manipulations.Human molecular genetics · 2025Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.Genetics · 2025Article
- Interaction between neuromuscular junction metabolic requirements in fragile X syndrome and glycogen storage disease models.Disease models & mechanisms · 2025Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.bioRxiv : the preprint server for biology · 2025Article
- Soy Protein Isolate Affects Blood and Brain Biomarker Expression in a Mouse Model of Fragile X.International journal of molecular sciences · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Do metabolic deficits contribute to sleep disruption in monogenic intellectual disability syndromes?Trends in neurosciences · 2024Review
- Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- From wings to whiskers to stem cells: why every model matters in fragile X syndrome research.Journal of neurodevelopmental disorders · 2024Review
- Tet controls axon guidance in early brain development through glutamatergic signaling.iScience · 2024Article
- PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome.npj metabolic health and disease · 2024Article
- Negative effect of treatment with mGluR5 negative allosteric modulator AFQ056 on blood biomarkers in young individuals with Fragile X syndrome.SAGE open medicine · 2024Article
- Longitudinal follow-up of metformin treatment in Fragile X Syndrome.Frontiers in psychology · 2024Article
- Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition.Molecular psychiatry · 2023Article
- Review
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2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.
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What Socratic holds
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 Socratic graph.