ArticlePLoS biology2013
Impairment of TrkB-PSD-95 signaling in Angelman syndrome.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers.
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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.
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Who cites it
105 citing papers in PubMed, 172 citations in OpenAlex.
- TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate microglial activation and alleviate depression-like behaviors in male mice.Molecular psychiatry · 2026Article
- Mechanistic insights into anti-parkinson effect of baicalein: from neuroinflammation and cell death to neurogenesis and synaptic plasticity.Molecular biology reports · 2026Review
- Neuroprotective potential of a TrkB-FL-derived cell-penetrating peptide in cochlear synaptopathy and noise-induced hearing loss.Molecular medicine (Cambridge, Mass.) · 2026Article
- Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome.bioRxiv : the preprint server for biology · 2026Article
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- HIF-1 Targeting Intervention Renders Protection From Alzheimer's-Like Pathology in a Humanized Mice Model of HIV Infection.Journal of extracellular vesicles · 2025Article
- Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome.Journal of neurodevelopmental disorders · 2025Article
- Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Human Virus-Like Proteins: Implications for Gene Therapy.Current gene therapy · 2025Review
- Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis.Current neurology and neuroscience reports · 2024Review
- Syn3, a newly developed cyclic peptide and BDNF signaling enhancer, ameliorates retinal ganglion cell degeneration in diabetic retinopathy.Protein & cell · 2024Article
- Interlinked destinies: How ubiquitin-proteasome and autophagy systems underpin neurocognitive outcomes.Experimental neurology · 2024Review
- Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.Science signaling · 2024Article
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- G protein subunit alpha i2's pivotal role in angiogenesis.Theranostics · 2024Article
- Structure-based design of peptidomimetic inhibitors of PSD-95 with improved affinity for the PDZ3 domain.FEBS letters · 2024Article
- Rett and Rett-related disorders: Common mechanisms for shared symptoms?Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.Cell death & disease · 2023Article
- Mechanisms and Functions of Activity-Regulated Cytoskeleton-Associated Protein in Synaptic Plasticity.Molecular neurobiology · 2023Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction.
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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.