ArticleEuropean journal of human genetics : EJHG2017
Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology.
Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling.Journal of neuroinflammation · 2025Article
- MeCP2 interacts with the super elongation complex to regulate transcription.Science advances · 2025Article
- A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex.Development (Cambridge, England) · 2025Article
- SIK1 Downregulates Synaptic AMPA Receptors and Contributes to Cognitive Defects in Alzheimer's Disease.Molecular neurobiology · 2024Article
- Role of SIK1 in tumors: Emerging players and therapeutic potentials (Review).Oncology reports · 2024Review
- Protective effects of the saltZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Blocking salt-inducible kinases with YKL-06-061 prevents PTZ-induced seizures in mice.Brain and behavior · 2023Article
- Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.Brain : a journal of neurology · 2023Article
- Mimicking Hypoxic-Ischemic Encephalopathy in a Newborn with 21q Deletion Originating from Ring Chromosome 21.Children (Basel, Switzerland) · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.Nature neuroscience · 2023Article
- The SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by microRNA-25-3p are altered in the schizophrenic rat brain.Frontiers in cellular neuroscience · 2023Article
- Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.Cells · 2022Review
- An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice.International journal of molecular sciences · 2022Article
- Novel mutation of SIK1 gene causing a mild form of pediatric epilepsy in a Chinese patient.Metabolic brain disease · 2022Article
- Progress on the roles of MEF2C in neuropsychiatric diseases.Molecular brain · 2022Review
- ATranslational pediatrics · 2021Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- Risperidone Mitigates Enhanced Excitatory Neuronal Function and Repetitive Behavior Caused by an ASD-Associated Mutation of SIK1.Frontiers in molecular neuroscience · 2021Article
- Salt inducible kinases as novel Notch interactors in the developing Drosophila retina.PloS one · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein. We evaluated the transcriptional activity of known downstream gene targets in neurons expressing mutant SIK1 compared with wild type. We then assayed neuronal morphology by measuring neurite length, number and branching. Truncating SIK1 sequence variations were associated with abnormal MEF2C transcriptional activity and decreased MEF2C protein levels. Epilepsy-causing SIK1 sequence variations were associated with significantly decreased expression of ARC (activity-regulated cytoskeletal-associated) and other synaptic activity response element genes. Assay of mRNA levels for other MEF2C target genes NR4A1 (Nur77) and NRG1, found significantly, decreased the expression of these genes as well. The missense p.(Pro287Thr) SIK1 sequence variation was associated with abnormal neuronal morphology, with significant decreases in mean neurite length, mean number of neurites and a significant increase in proximal branches compared with wild type. Epilepsy-causing SIK1 sequence variations resulted in abnormalities in the MEF2C-ARC pathway of neuronal development and synapse activity response. This work provides the first insights into the mechanisms of pathogenesis in SIK1 syndrome, and extends the ARX-MEF2C pathway in the pathogenesis of developmental epilepsy.
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