ArticleNeuron2014
MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 58 citations in OpenAlex.
- The small molecule simufilam dose-dependently attenuates the worsening of seizures in a mouse model of tuberous sclerosis complex.Epilepsia · 2026Article
- Beyond mTOR: Unraveling the Complex Pathophysiology and Signaling Pathways in Focal Cortical Dysplasia.Molecular neurobiology · 2025Review
- Machine Learning Identifies FLNA as a Key Molecular Target Regulating Neuronal Apoptosis after Spinal Cord Injury.Journal of molecular neuroscience : MN · 2025Article
- Filamin A in focus: unravelling the multifaceted roles of filamin A in neurodevelopment and neurological disorders.Brain : a journal of neurology · 2025Review
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- Advancements in Surgical Therapies for Drug-Resistant Epilepsy: A Paradigm Shift towards Precision Care.Neurology and therapy · 2025Review
- Focal cortical dysplasia type II: review of neuropathological manifestations and pathogenetic mechanisms.Acta epileptologica · 2025Review
- Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Charting the importance of filamin A posttranslational modifications.The Biochemical journal · 2024Review
- Direct and Indirect Effects of Filamin A on Tau Pathology in Neuronal Cells.Molecular neurobiology · 2023Article
- Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology.Science advances · 2022Article
- Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex.Epilepsy research · 2022Article
- Evidence of Filamin A loss of solubility at the prodromal stage of neuropathologically-defined Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
- Article
- The Coordination of mTOR Signaling and Non-Coding RNA in Regulating Epileptic Neuroinflammation.Frontiers in immunology · 2022Review
- Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis.JCI insight · 2021Article
- Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission.International journal of molecular sciences · 2021Review
- Small Extracellular Vesicles Control Dendritic Spine Development through Regulation of HDAC2 Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Article
- Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies.Frontiers in neuroanatomy · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Abnormal dendritic complexity is a shared feature of many neurodevelopmental disorders associated with neurological defects. Here, we found that the actin-crosslinking protein filamin A (FLNA) is overexpressed in tuberous sclerosis complex (TSC) mice, a PI3K-mTOR model of neurodevelopmental disease that is associated with abnormal dendritic complexity. Both under- and overexpression of FLNA in wild-type neurons led to more complex dendritic arbors in vivo, suggesting that an optimal level of FLNA expression is required for normal dendritogenesis. In Tsc1(null) neurons, knocking down FLNA in vivo prevented dendritic abnormalities. Surprisingly, FLNA overexpression in Tsc1(null) neurons was dependent on MEK1/2 but not mTOR activity, despite both pathways being hyperactive. In addition, increasing MEK-ERK1/2 activity led to dendritic abnormalities via FLNA, and decreasing MEK-ERK1/2 signaling in Tsc1(null) neurons rescued dendritic defects. These data demonstrate that altered FLNA expression increases dendritic complexity and contributes to pathologic dendritic patterning in TSC in an mTOR-independent, ERK1/2-dependent manner.
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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.