ArticleBrain pathology (Zurich, Switzerland)2019
CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling.
Article in Brain pathology (Zurich, Switzerland), 2019. 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 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- CDKL5 regulates the initiation of retrograde axonal transport through CLIP170-dynactin complex formation.The FEBS journal · 2026Article
- Shared Disease Mechanisms in Neurodevelopmental Disorders: A Cellular and Molecular Biology Perspective.Brain sciences · 2025Review
- Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer's Disease.Research square · 2025Article
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- CDKL5 Deficiency Disorder: Revealing the Molecular Mechanism of Pathogenic Variants.International journal of molecular sciences · 2025Article
- Adult-Onset Deletion of CDKL5 in Forebrain Glutamatergic Neurons Impairs Synaptic Integrity and Behavior in Mice.International journal of molecular sciences · 2025Article
- Transcriptomic Profiling of Zebrafish Mutant forInternational journal of molecular sciences · 2025Article
- Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy.Journal of cellular and molecular medicine · 2025Article
- A cross-correction gene therapy approach for CDKL5 deficiency disorder improves the pathological phenotype of CDD patient-derived cortical organoids.Frontiers in bioengineering and biotechnology · 2025Article
- Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.Journal of neurodevelopmental disorders · 2024Article
- Novel CDKL5 targets identified in human iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2024Article
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Voluntary Running Improves Behavioral and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder.Biomolecules · 2023Article
- Research progress on the pathogenesis of CDKL5 pathogenic variants and related encephalopathy.European journal of pediatrics · 2023Review
- CDKL5 deficiency disorder: molecular insights and mechanisms of pathogenicity to fast-track therapeutic development.Biochemical Society transactions · 2022Review
- Luteolin Treatment Ameliorates Brain Development and Behavioral Performance in a Mouse Model of CDKL5 Deficiency Disorder.International journal of molecular sciences · 2022Article
- Altered network and rescue of human neurons derived from individuals with early-onset genetic epilepsy.Molecular psychiatry · 2021Article
- Inhibition of microglia overactivation restores neuronal survival in a mouse model of CDKL5 deficiency disorder.Journal of neuroinflammation · 2021Article
- Age-Related Cognitive and Motor Decline in a Mouse Model of CDKL5 Deficiency Disorder is Associated with Increased Neuronal Senescence and Death.Aging and disease · 2021Article
Corrections and comments
- Erratum issuedCorrigendum.2020
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDKL5 deficiency disorder (CDD) is a rare encephalopathy characterized by early onset epilepsy and severe intellectual disability. CDD is caused by mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene, a member of a highly conserved family of serine-threonine kinases. Only a few physiological substrates of CDKL5 are currently known, which hampers the discovery of therapeutic strategies for CDD. Here, we show that SMAD3, a primary mediator of TGF-β action, is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes SMAD3 protein stability. Importantly, we found that restoration of the SMAD3 signaling through TGF-β1 treatment normalized defective neuronal survival and maturation in Cdkl5 knockout (KO) neurons. Moreover, we demonstrate that Cdkl5 KO neurons are more vulnerable to neurotoxic/excitotoxic stimuli. In vivo treatment with TGF-β1 prevents increased NMDA-induced cell death in hippocampal neurons from Cdkl5 KO mice, suggesting an involvement of the SMAD3 signaling deregulation in the neuronal susceptibility to excitotoxic injury of Cdkl5 KO mice. Our finding reveals a new function for CDKL5 in maintaining neuronal survival that could have important implications for susceptibility to neurodegeneration in patients with CDD.
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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.