ArticleFrontiers in pharmacology2020
Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia.
Article in Frontiers in pharmacology, 2020. 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, 30 citations in OpenAlex.
- mTOR-driven autophagy-inflammation crosstalk underlies schizophrenia pathophysiology.Translational psychiatry · 2026Article
- Extracellular matrix dysfunction and synaptic alterations in schizophrenia.Molecular psychiatry · 2026Article
- Protein Kinase Expression of the AKT/mTOR Signaling Pathway in Peripheral Mononuclear Cells of Schizophrenia Patients: A Pilot Study.NeuroSci · 2025Article
- Epigenetic Mechanisms Shaping Spine Regulation: Unveiling the Role of Cytoskeletal Dynamics and Localized Protein Synthesis.Molecular neurobiology · 2025Review
- The Inflammatory Nexus: Unraveling Shared Pathways and Promising Treatments in Alzheimer's Disease and Schizophrenia.International journal of molecular sciences · 2025Review
- Following the Action of Atypical Antipsychotic Clozapine and Possible Prediction of Treatment Response in Schizophrenia.Life (Basel, Switzerland) · 2025Review
- Neuronal alterations in AKT isotype expression in schizophrenia.Molecular psychiatry · 2025Article
- Neuronal alterations in AKT isotype expression in schizophrenia.Research square · 2024Article
- PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?The international journal of neuropsychopharmacology · 2024Review
- DPYSL2/CRMP2 isoform B knockout in human iPSC-derived glutamatergic neurons confirms its role in mTOR signaling and neurodevelopmental disorders.Molecular psychiatry · 2023Article
- The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy.Psychopharmacology · 2023Article
- GSK3β and mTORC1 Represent 2 Distinct Signaling Markers in Peripheral Blood Mononuclear Cells of Drug-Naive, First Episode of Psychosis Patients.Schizophrenia bulletin · 2022Article
- HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk.Viruses · 2022Article
- Molecular Features Triggered by Antipsychotic Medication in Brain Cells.Advances in experimental medicine and biology · 2022Article
- It takes two to tango: Widening our understanding of the onset of schizophrenia from a neuro-angiogenic perspective.Frontiers in cell and developmental biology · 2022Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- mTOR kinase activity disrupts a phosphorylation signaling network in schizophrenia brain.Molecular psychiatry · 2021Article
- Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells.International journal of molecular sciences · 2021Article
- Cannabis Use Induces Distinctive Proteomic Alterations in Olfactory Neuroepithelial Cells of Schizophrenia Patients.Journal of personalized medicine · 2021Article
- Transcriptomics Analysis Reveals Shared Pathways in Peripheral Blood Mononuclear Cells and Brain Tissues of Patients With Schizophrenia.Frontiers in psychiatry · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin (also known as mammalian target of rapamycin) (mTOR)-dependent signaling pathway plays an important role in protein synthesis, cell growth, and proliferation, and has been linked to the development of the central nervous system. Recent studies suggest that mTOR signaling pathway dysfunction could be involved in the etiopathogenesis of schizophrenia. The main goal of this study was to evaluate the status of mTOR signaling pathway in postmortem prefrontal cortex (PFC) samples of subjects with schizophrenia. For this purpose, we quantified the protein expression and phosphorylation status of the mTOR downstream effector ribosomal protein S6 as well as other pathway interactors such as Akt and GSK3β. Furthermore, we quantified the status of these proteins in the brain cortex of rats chronically treated with the antipsychotics haloperidol, clozapine, or risperidone. We found a striking decrease in the expression of total S6 and in its active phosphorylated form phospho-S6 (Ser235/236) in the brain of subjects with schizophrenia compared to matched controls. The chronic treatment with the antipsychotics haloperidol and clozapine affected both the expression of GSK3β and the activation of Akt [phospho-Akt (Ser473)] in rat brain cortex, while no changes were observed in S6 and phospho-S6 (Ser235/236) protein expression with any antipsychotic treatment. These findings provide further evidence for the involvement of the mTOR-dependent signaling pathway in schizophrenia and suggest that a hypofunctional S6 may have a role in the etiopathogenesis of this disorder.
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