ArticleScience translational medicine2016
MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
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- Suppressing DUSP16 overexpression induced by ELK1 promotes neural progenitor cell differentiation in mouse models of Alzheimer's disease.Aging cell · 2025Article
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults.The journal of prevention of Alzheimer's disease · 2024Article
- Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway.Nature communications · 2023Article
- Blockade of Type 2A Protein Phosphatase Signaling Attenuates Complement C1q-Mediated Microglial Phagocytosis of Glutamatergic Synapses Induced by Amyloid Fibrils.Molecular neurobiology · 2023Article
- BOMA, a machine-learning framework for comparative gene expression analysis across brains and organoids.Cell reports methods · 2023Article
- TRRAP-mediated acetylation on Sp1 regulates adult neurogenesis.Computational and structural biotechnology journal · 2023Article
- FMRP modulates the Wnt signalling pathway in glioblastoma.Cell death & disease · 2022Article
- Maturation Delay of Human GABAergic Neurogenesis in Fragile X Syndrome Pluripotent Stem Cells.Stem cells translational medicine · 2022Article
- Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of fragile X syndrome.BMC medicine · 2022Article
- FMRP ligand circZNF609 destabilizes RAC1 mRNA to reduce metastasis in acral melanoma and cutaneous melanoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
- ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model.Neurobiology of disease · 2021Article
- In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker.Scientific reports · 2021Article
- Formation and integration of new neurons in the adult hippocampus.Nature reviews. Neuroscience · 2021Review
- sncRiboTag-Seq: cell-type-specific RiboTag-Seq for cells in low abundance in mouse brain tissue.STAR protocols · 2021Article
- Local Translation in Perisynaptic Astrocytic Processes Is Specific and Changes after Fear Conditioning.Cell reports · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome.
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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.