ArticleCell & bioscience2022
AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Desloratadine Rescues Schizophrenia-like Phenotypes by Inhibiting the Pathogenic 5-HT2AR-PI3K/AKT/mTOR Signaling Axis.Molecular neurobiology · 2026Article
- Identifying drug targets for schizophrenia through gene prioritization.Translational psychiatry · 2026Article
- Warfarin and bevacizumab suppress tumor progression in pancreatic ductal adenocarcinoma by targeting EGFR-PI3K-Akt signaling: inhibition of proliferation/migration and apoptosis induction.Translational cancer research · 2025Article
- Effects of Risperidone and Aripiprazole Antipsychotic Drugs on Behavioral Changes and the Expression Levels of DRD2, HTR2A, AKT1, and CACNA1C Genes in the Hippocampus of a Ketamine-induced Schizophrenia-like Rat Model.Journal of molecular neuroscience : MN · 2025Article
- Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis.European journal of medical research · 2025Article
- p70S6K as a Potential Anti-COVID-19 Target: Insights from Wet Bench and In Silico Studies.Cells · 2024Article
- Article
- Single-cell genomics and regulatory networks for 388 human brains.Science (New York, N.Y.) · 2024Article
- Article
- Single-cell genomics and regulatory networks for 388 human brains.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive analysis of circRNA expression profile and circRNA-miRNA-mRNA network susceptibility to very early-onset schizophrenia.Schizophrenia (Heidelberg, Germany) · 2023Article
- Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish.Nature communications · 2023Article
- Genetic polymorphism and neuroanatomical changes in schizophrenia.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologieReview
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundChanges in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.
methods(1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms (SNPs) in the AKT3 gene. (3) We analyzed the psychiatric adverse events (AEs) of patients treated with M2698 (p70S6K/AKT1/AKT3 inhibitor) and with other PI3K/AKT/mTOR pathway inhibitors.
results(1) Proteins encoded by AKT3 (AKT3Q60H) and AKT1 (AKT1Q61H) mutants had lower kinase activity than those encoded by wild-type AKT3 and AKT1, respectively. Molecular modeling of the AKT1-Q61H mutant suggested conformational changes that may reduce the binding of D3-phosphorylated phosphoinositides to the PH domain. (2) We identified multiple SNPs in the AKT3 gene that were strongly associated with schizophrenia (p < 0.5 × 10
conclusionsOur data elucidate the incidence and mechanisms of psychiatric AEs in patients treated with PI3K/AKT/mTOR inhibitors and emphasize the need for careful monitoring.
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