ArticleMolecular omics2019
Kinase network dysregulation in a human induced pluripotent stem cell model of DISC1 schizophrenia.
Article in Molecular omics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- DISC1 Protects Against Zika Virus Infection and Long-Term Neurological Damage Through AMPK-mTOR-Mediated Autophagy.Nature communications · 2025Article
- Analyses of GWAS and Sub-Threshold Loci Lead to the Discovery of Dendrite Development and Morphology Dysfunction Underlying Schizophrenia Genetic Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multi-Omic Analysis of Glutamate Excitotoxicity in Primary Neuronal Cultures.Journal of neurochemistry · 2025Article
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Non-Invasive Quality Control of Organoid Cultures Using Mesofluidic CSTR Bioreactors and High-Content Imaging.Advanced materials technologies · 2025Article
- Article
- In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.Science advances · 2024Article
- Defined co-cultures of glutamatergic and GABAergic neurons with a mutation in DISC1 reveal aberrant phenotypes in GABAergic neurons.BMC neuroscience · 2024Article
- Article
- Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023Article
- Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells.Acta neuropathologica communications · 2022Review
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Article
- Subcellular partitioning of protein kinase activity revealed by functional kinome profiling.Scientific reports · 2022Article
- Connecting omics signatures and revealing biological mechanisms with iLINCS.Nature communications · 2022Article
- Multi-Omics Characterization of Early- and Adult-Onset Major Depressive Disorder.Journal of personalized medicine · 2022Article
- Mutations in DISC1 alter IPNeuronal signaling · 2021Review
- mTOR kinase activity disrupts a phosphorylation signaling network in schizophrenia brain.Molecular psychiatry · 2021Article
- Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages.International journal of molecular sciences · 2021Article
- Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter.Molecular psychiatry · 2021Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
Protein kinases orchestrate signal transduction pathways involved in central nervous system functions ranging from neurodevelopment to synaptic transmission and plasticity. Abnormalities in kinase-mediated signaling are involved in the pathophysiology of neurological disorders, including neuropsychiatric disorders. Here, we expand on the hypothesis that kinase networks are dysregulated in schizophrenia. We investigated changes in serine/threonine kinase activity in cortical excitatory neurons differentiated from induced pluripotent stem cells (iPSCs) from a schizophrenia patient presenting with a 4 bp mutation in the disrupted in schizophrenia 1 (DISC1) gene and a corresponding control. Using kinome peptide arrays, we demonstrate large scale abnormalities in DISC1 cells, including a global depression of serine/threonine kinase activity, and changes in activity of kinases, including AMP-activated protein kinase (AMPK), extracellular signal-regulated kinases (ERK), and thousand-and-one amino acid (TAO) kinases. Using isogenic cell lines in which the DISC1 mutation is either introduced in the control cell line, or rescued in the schizophrenia cell line, we ascribe most of these changes to a direct effect of the presence of the DISC1 mutation. Investigating the gene expression signatures downstream of the DISC1 kinase network, and mapping them on perturbagen signatures obtained from the Library of Integrated Network-based Cellular Signatures (LINCS) database, allowed us to propose novel drug targets able to reverse the DISC1 kinase dysregulation gene expression signature. Altogether, our findings provide new insight into abnormalities of kinase networks in schizophrenia and suggest possible targets for disease intervention.
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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.