ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Targeting Translation Control with p70 S6 Kinase 1 Inhibitors to Reverse Phenotypes in Fragile X Syndrome Mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome.Journal of neurodevelopmental disorders · 2020Trial
- RNF168 dephosphorylation ameliorates cognitive decline in Aβ-based mouse models of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Inhibition of p70 Ribosomal S6 Kinase (S6K1) Reduces Cortical Blood Flow in a Rat Model of Autism-Tuberous Sclerosis.Neuromolecular medicine · 2024Article
- Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice.Cell reports · 2023Article
- Quantitative proteomics and phosphoproteomics of PPP2R5D variants reveal deregulation of RPS6 phosphorylation through converging signaling cascades.bioRxiv : the preprint server for biology · 2023Article
- Article
- Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice.Brain : a journal of neurology · 2022Article
- Vorinostat Corrects Cognitive and Non-Cognitive Symptoms in a Mouse Model of Fragile X Syndrome.The international journal of neuropsychopharmacology · 2022Article
- Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function.Molecular psychiatry · 2021Article
- Cell-type-specific profiling of human cellular models of fragile X syndrome reveal PI3K-dependent defects in translation and neurogenesis.Cell reports · 2021Article
- Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks.Molecular psychiatry · 2020Article
- Excessive Homeostatic Gain in Spinal Motoneurons in a Mouse Model of Amyotrophic Lateral Sclerosis.Scientific reports · 2020Article
- Preclinical testing of the ketogenic diet in fragile X mice.Neurochemistry international · 2020Article
- Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders.Frontiers in cellular neuroscience · 2020Review
- Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity.Cells · 2019Article
- Kinase pathway inhibition restores PSD95 induction in neurons lacking fragile X mental retardation protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular Biomarkers in Fragile X Syndrome.Brain sciences · 2019Review
- Altered steady state and activity-dependent de novo protein expression in fragile X syndrome.Nature communications · 2019Article
- Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Aberrant neuronal translation is implicated in the etiology of numerous brain disorders. Although mTORC1-p70 ribosomal S6 kinase 1 (S6K1) signaling is critical for translational control, pharmacological manipulation in vivo has targeted exclusively mTORC1 due to the paucity of specific inhibitors to S6K1. However, small molecule inhibitors of S6K1 could potentially ameliorate pathological phenotypes of diseases, which are based on aberrant translation and protein expression. One such condition is fragile X syndrome (FXS), which is considered to be caused by exaggerated neuronal translation and is the most frequent heritable cause of autism spectrum disorder (ASD). To date, potential therapeutic interventions in FXS have focused largely on targets upstream of translational control to normalize FXS-related phenotypes. Here we test the ability of two S6K1 inhibitors, PF-4708671 and FS-115, to normalize translational homeostasis and other phenotypes exhibited by FXS model mice. We found that although the pharmacokinetic profiles of the two S6K1 inhibitors differed, they overlapped in reversing multiple disease-associated phenotypes in FXS model mice including exaggerated protein synthesis, inappropriate social behavior, behavioral inflexibility, altered dendritic spine morphology, and macroorchidism. In contrast, the two inhibitors differed in their ability to rescue stereotypic marble-burying behavior and weight gain. These findings provide an initial pharmacological characterization of the impact of S6K1 inhibitors in vivo for FXS, and have therapeutic implications for other neuropsychiatric conditions involving aberrant mTORC1-S6K1 signaling.
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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.