ArticleThe Journal of clinical investigation2015
PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- The genetic architecture of brainstem structures.Nature communications · 2025Pooled it
- Ganaxolone, an approved therapy for CDKL5-deficiency disorder, is an inhibitor of PTP1B.The Journal of biological chemistry · 2026Article
- Inhibition of protein tyrosine phosphatase PTP1B function ameliorates pathophysiological deficits in Rett Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Enhanced expression of spinal PTP1B contributes to peripheral inflammation- induced glycinergic disinhibition and mechanical pain.Communications biology · 2026Article
- Shifting paradigms: phosphatases from basic biology to druggable targets.Biology open · 2026Article
- PTP1B inhibition promotes microglial phagocytosis in Alzheimer's disease models by enhancing SYK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Network Pharmacology, Molecular Docking and Molecular Dynamics Studies to Predict the Molecular Targets and Mechanisms of Action ofPlants (Basel, Switzerland) · 2025Article
- Exploring the Therapeutic Potential of Glycyrrhiza Compounds in Alzheimer's Disease: A Comprehensive Review.Current topics in medicinal chemistry · 2025Review
- Exploring the Antidiabetic Potential ofPlants (Basel, Switzerland) · 2024Article
- An expanded trove of fragment-bound structures for the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data.Structure (London, England : 1993) · 2024Article
- Multireceptor Analysis for Evaluating the Antidiabetic Efficacy of Karanjin: A Computational Approach.Endocrinology, diabetes & metabolism · 2024Article
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- An expanded view of ligandability in the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data.bioRxiv : the preprint server for biology · 2024Article
- Sodium orthovanadate exhibits anti-angiogenic, antiapoptotic and blood glucose-lowering effect on colon cancer associated with diabetes.Cancer chemotherapy and pharmacology · 2024Article
- Enzyme PTP-1B Inhibition Studies by Vanadium Metal Complexes: a Kinetic Approach.Biological trace element research · 2023Article
- Licochalcone A: A Potential Multitarget Drug for Alzheimer's Disease Treatment.International journal of molecular sciences · 2023Review
- Protein Tyrosine Phosphatases: Mighty oaks from little acorns grow.IUBMB life · 2023Article
- A novel rhein-huprine hybrid ameliorates disease-modifying properties in preclinical mice model of Alzheimer's disease exacerbated with high fat diet.Cell & bioscience · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.
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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.