ArticleMolecular neurobiology2020
Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons.
Article in Molecular neurobiology, 2020. 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 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Ganaxolone, an approved therapy for CDKL5-deficiency disorder, is an inhibitor of PTP1B.The Journal of biological chemistry · 2026Article
- Disruption of DNA Repair as an Emerging Epigenetic Mechanism Underlying Autism Spectrum Disorder.Current psychiatry reports · 2026Review
- Endocannabinoid Enhancement via MAGL Inhibition in CDKL5 Deficiency: Selective Cellular Benefits and Domain-Specific Functional Effects in AdultInternational journal of molecular sciences · 2026Article
- Probing DNA damage in Rett syndrome neurons uncovers a role for MECP2 regulation of PARP1.Stem cell reports · 2025Article
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Beneficial Antioxidant Effects of Coenzyme Q10 in In Vitro and In Vivo Models of CDKL5 Deficiency Disorder.International journal of molecular sciences · 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
- Rett and Rett-related disorders: Common mechanisms for shared symptoms?Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Voluntary Running Improves Behavioral and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder.Biomolecules · 2023Article
- Selected Biomarkers of Oxidative Stress and Energy Metabolism Disorders in Neurological Diseases.Molecular neurobiology · 2023Review
- Research progress on the pathogenesis of CDKL5 pathogenic variants and related encephalopathy.European journal of pediatrics · 2023Review
- A Novel Methodology Using Dexamethasone to Induce Neuronal Differentiation in the CNS-Derived Catecholaminergic CAD Cells.Cellular and molecular neurobiology · 2022Article
- 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
- 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
- Treatment with a GSK-3β/HDAC Dual Inhibitor Restores Neuronal Survival and Maturation in an In Vitro and In Vivo Model ofInternational journal of molecular sciences · 2021Article
- Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the CDKL5 gene, which encodes a serine/threonine kinase, causes a rare encephalopathy, characterized by early-onset epilepsy and severe intellectual disability, named CDKL5 deficiency disorder (CDD). In vitro and in vivo studies in mouse models of Cdkl5 deficiency have highlighted the role of CDKL5 in brain development and, in particular, in the morphogenesis and synaptic connectivity of hippocampal and cortical neurons. Interestingly, Cdkl5 deficiency in mice increases vulnerability to excitotoxic stress in hippocampal neurons. However, the mechanism by which CDKL5 controls neuronal survival is far from being understood. To investigate further the function of CDKL5 and dissect the molecular mechanisms underlying neuronal survival, we generated a human neuronal model of CDKL5 deficiency, using CRISPR/Cas9-mediated genome editing. We demonstrated that CDKL5 deletion in human neuroblastoma SH-SY5Y cells not only impairs neuronal maturation but also reduces cell proliferation and survival, with alterations in the AKT and ERK signaling pathways and an increase in the proapoptotic BAX protein and in DNA damage-associated biomarkers (i.e., γH2AX, RAD50, and PARP1). Furthermore, CDKL5-deficient cells were hypersensitive to DNA damage-associated stress, accumulated more DNA damage foci (γH2AX positive) and were more prone to cell death than the controls. Importantly, increased kainic acid-induced cell death of hippocampal neurons of Cdkl5 KO mice correlated with an increased γH2AX immunostaining. The results suggest a previously unknown role for CDKL5 in DNA damage response that could underlie the pro-survival function of CDKL5.
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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.