AKT1 and genetic vulnerability to bipolar disorder

Millischer, Vincent; Matheson, Granville J.; Martinsson, Lina; Ek, Inger Römer; Schalling, Martin; Lavebratt, Catharina; Backlund, Lena

doi:10.1016/j.psychres.2019.112677

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…AKT1 was a first-line target for treatment of BD (Beaulieu, 2012). Although a recent cohort study contradicted the relationship between AKT1 and BD (Millischer et al, 2020), the correlation with the occurrence of depression was certain. AKT1 participates in the myelination of the peripheral nervous system and neurotrophic protein signaling pathway: the AKT/mTOR pathway may be the common core target of psychoactive drugs (Musashe et al, 2016;Liu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Systematic review of Kaixinsan in treating depression: Efficacy and pharmacological mechanisms

Zhang

et al. 2022

Front. Behav. Neurosci.

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IntroductionKaixinsan (KXS) has been in use as an effective classic formulation of traditional Chinese medicine for depression. However, its active components and action mechanism against depression remain elusive. The purpose of this study was to summarize and evaluate the efficacy and potential pharmacological mechanisms of KXS in antidepressant treatment.Materials and methodsReports on the use of KXS in the treatment of depression were systematically collected from PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Data from the establishment to July 2022, including those on mood disorders in neurological diseases such as Alzheimer’s disease. Meta-analysis was conducted with the Review Manager 5.3 software. Online datasets, traditional Chinese medicine system pharmacological analysis platform, GeneCards, online Mendelian inheritance in man, and DisGeNET were used to investigate the depression-related genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were performed to construct the ‘component-target-pathways’ network using Metascape online analyses.ResultTen studies were included in the analysis. Meta-analysis showed that both low-dose KXS (SMD = 19.66, Z = 7.96, and I2 = 42%) and high-dose KXS (SMD = 23.84, Z = 8.46, and I2 = 13%) could increase the sucrose preference in depression models. In addition, 5-hydroxytryptamine (5-HT) (SMD = 10.91, Z = 2.95, and I2 = 50%) returned to normal level after the treatment at low dose KXS. In network pharmacology, 50 active components and 376 gene targets were screened out. AKT1, GAPDH, ALB, TNF, and TP53 were the core target proteins. GO analysis showed that KXS mainly treats depression in biological processes such as response to drugs, cellular calcium ion homeostasis, and regulation of chemical synaptic signal transmission. KEGG results show that the mechanism of action of KXS in treating depression is through neural activity ligand-receptor interaction, the calcium signaling and CAMP signaling pathways.DiscussionThe study reveals the active components and potential molecular mechanism of KXS in the treatment of depression and provides evidence for future basic research.

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Section: Discussionmentioning

confidence: 99%

Systematic review of Kaixinsan in treating depression: Efficacy and pharmacological mechanisms

Zhang

et al. 2022

Front. Behav. Neurosci.

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“…Akt belongs to serine/threonine protein kinase, an important target downstream of PI3K. As its most important subtype, Akt1 participates in numerous BP, including cell survival, proliferation and apoptosis, neovascularization, and cell cycle regulation, and has been explored in studies on depression since its polymorphism was found to be is related to the severity of depression, anxiety symptoms, suicidal tendencies, and so on (37)(38)(39). TNF is a cytokine that constitutes the acute phase response and is involved in systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Chaihu Longgu oyster adjusted decoction for the treatment of depression based on network pharmacology and molecular docking technology

Li¹,

Li²,

Liu³

et al. 2023

Ann Transl Med

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Background: Depression is a common clinical psychiatric disorder that is responsible for health-related disease burdens globally. According to traditional Chinese medicine (TCM), mental disorders and qi stagnation are important pathogenic mechanisms of depression. The Chaihu Longgu Oyster Decoction, which has been documented in the Shanghanlun (Treatise on Typhoid), is widely used to treat various affective disorders. Methods: Network pharmacology and molecular docking technology were used to investigate the material basis and mechanism of action of the Chaihu Longgu oyster adjusted decoction in treating depression. The main pharmacological substance bases, possible targets, and pathways of Chaihu Longgu oyster adjusted decoction in treating depression were visualized by constructing a "component-pathway-target" network. Results: Quercetin, 7-methoxy-2-methylisoflavone, baicalein, kaempferol, and lignan are the main practical chemical components in Chaihu Longgu oyster adjusted decoction. The Chaihu Longgu oyster adjusted decoction regulates 74 protein targets and 142 pathways associated with depression. Its molecular mechanism involves inhibiting neuroinflammation and improving neurotransmitter function, neuroplasticity, etc. Conclusions: The underlying mechanism of the anti-depressive effect of the Chaihu Longgu oyster adjusted decoction may involve neuroinflammatory response reduction and improvement of neurotransmitter function and neuroplasticity. This study revealed the mechanism of action of the Chaihu Longgu oyster adjusted decoction in the treatment of depression through network pharmacology, which provides a scientific basis for clinical application.

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“…Network analysis showed that AKT1, VEGFA and EGFR were the key targets of ginsenoside Rg1 for enabling anti-fatigue effects. AKT1 encodes serine/threonine kinases that play an important role in several normal and pathological cell processes ( Millischer et al, 2020 ), and a deficiency in AKT1 increases energy consumption ( Wan et al, 2012 ). A randomized controlled trial found that AKT1 is an important core target for the treatment of cancer-induced fatigue ( Cui et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism

et al. 2023

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Background: Chronic fatigue syndrome (CFS) is characterized by significant and persistent fatigue. Ginseng is a traditional anti-fatigue Chinese medicine with a long history in Asia, as demonstrated by clinical and experimental studies. Ginsenoside Rg1 is mainly derived from ginseng, and its anti-fatigue metabolic mechanism has not been thoroughly explored.Methods: We performed non-targeted metabolomics of rat serum using LC-MS and multivariate data analysis to identify potential biomarkers and metabolic pathways. In addition, we implemented network pharmacological analysis to reveal the potential target of ginsenoside Rg1 in CFS rats. The expression levels of target proteins were measured by PCR and Western blotting.Results: Metabolomics analysis confirmed metabolic disorders in the serum of CFS rats. Ginsenoside Rg1 can regulate metabolic pathways to reverse metabolic biases in CFS rats. We found a total of 34 biomarkers, including key markers Taurine and Mannose 6-phosphate. AKT1, VEGFA and EGFR were identified as anti-fatigue targets of ginsenoside Rg1 using network pharmacological analysis. Finally, biological analysis showed that ginsenoside Rg1 was able to down-regulate the expression of EGFR.Conclusion: Our results suggest ginsenoside Rg1 has an anti-fatigue effect, impacting the metabolism of Taurine and Mannose 6-phosphate through EGFR regulation. This demonstrates ginsenoside Rg1 is a promising alternative treatment for patients presenting with chronic fatigue syndrome.

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AKT1 and genetic vulnerability to bipolar disorder

Cited by 8 publications

References 30 publications

Systematic review of Kaixinsan in treating depression: Efficacy and pharmacological mechanisms

Systematic review of Kaixinsan in treating depression: Efficacy and pharmacological mechanisms

Mechanism of Chaihu Longgu oyster adjusted decoction for the treatment of depression based on network pharmacology and molecular docking technology

Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism

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