ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- From brain bioenergetics to hypothalamic glucoregulation: A shared-systems hypothesis for intrinsic dysglycemia in schizophrenia.Reviews in endocrine & metabolic disorders · 2026Review
- Castl: robust identification of spatially variable genes in spatial transcriptomics via an ensemble-based framework.Briefings in bioinformatics · 2026Article
- Systems biology insights into the molecular drivers of childhood stunting and implications for intervention.Frontiers in nutrition · 2026Review
- Autophagy and Neuropsychiatric Disorders: Unraveling Molecular Mechanisms and Signaling Pathways.CNS & neurological disorders drug targets · 2026Review
- Neuroprotective effects ofFrontiers in molecular biosciences · 2026Article
- Sevoflurane Exposure Exacerbates Memory Impairment and Pathological Manifestation by Inhibiting AKT/mTOR-Mediated Autophagy in P301L Tau Transgenic Mice.CNS neuroscience & therapeutics · 2025Article
- Unraveling the mysteries of schizophrenia: Insights into prefrontal cortex dysfunction and therapeutic implications.World journal of psychiatry · 2025Review
- Protein Kinase Expression of the AKT/mTOR Signaling Pathway in Peripheral Mononuclear Cells of Schizophrenia Patients: A Pilot Study.NeuroSci · 2025Article
- Differential Effects of Prenatal Poly I:C Exposure and Antipsychotics on NMDA/GABA Receptors and GSK3β-Mediated Signaling in the Dorsal Raphe Nucleus of Female Rats.Fundamental & clinical pharmacology · 2025Article
- Translating Molecular Psychiatry: From Biomarkers to Personalized Therapies-A Narrative Review.International journal of molecular sciences · 2025Review
- Neuronal alterations in AKT isotype expression in schizophrenia.Molecular psychiatry · 2025Article
- An increased copy number of glycine decarboxylase (GLDC) associated with psychosis reduces extracellular glycine and impairs NMDA receptor function.Molecular psychiatry · 2025Article
- Psychedelics and schizophrenia: a double-edged sword.Molecular psychiatry · 2025Review
- "RNSP (Rannasangpei)" Rescued MK-801-induced Schizophrenia-like Behaviors in Mice via Oxidative Stress and BDNF-TrkB/Akt Pathway.Molecular neurobiology · 2024Article
- One path, two solutions: Network-based analysis identifies targetable pathways for the treatment of comorbid type II diabetes and neuropsychiatric disorders.Computational and structural biotechnology journal · 2024Article
- Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets.Psychopharmacology · 2024Review
- GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress.Cellular signalling · 2024Article
- 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
- Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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Abstract
Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness may be associated with dysregulation of core intracellular processes such as signaling pathways that underlie the regulation and integration of these systems. The AKT-mTOR signaling cascade has been implicated in SZ by gene association, postmortem brain and animal studies. AKT and mTOR are serine/threonine kinases which play important roles in cell growth, proliferation, survival, and differentiation. Both AKT and mTOR require phosphorylation at specific sites for their complete activation. mTOR forms two functionally distinct multiprotein complexes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2). mTORC1 mediates ribosome biogenesis, protein translation, and autophagy, whereas mTORC2 contributes to actin dynamics. Altered protein synthesis and actin dynamics can lead to an abnormal neuronal morphology resulting in deficits in learning and memory. Currently, there is a lack of direct evidence to support the hypothesis of disrupted mTOR signaling in SZ, and we have addressed this by characterizing this signaling pathway in SZ brain. We found a reduction in AKT and mTOR protein expression and/or phosphorylation state in dorsolateral prefrontal cortex (DLPFC) from 22 pairs of SZ and matched comparison subjects. We also found reduced protein expression of GβL, a subunit protein common to both mTOR complexes. We further investigated mTOR complex-specific subunit composition and phosphorylation state, and found abnormal mTOR expression in both complexes in SZ DLPFC. These findings provide evidence that proteins associated with the AKT-mTOR signaling cascade are downregulated in SZ DLPFC.
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