Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of the AKT and ERK signaling pathways

Pan, Yi; Wang, Wei Hsun; Huang, Teng-Hao; Weng, Wei; Fang, Cheng; Chen, Yu Chan; Hwang, Jeng Jong

doi:10.1007/s00011-018-1176-1

Cited by 13 publications

(8 citation statements)

References 46 publications

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“…A well-known antifungal agent, itraconazole, has demonstrated anticancer activity in various cell lines by inhibiting Akt/mTOR signaling ( 125 ). Quetiapine, an atypical antipsychotic, decreases the level of certain pro-inflammatory cytokines, such as interleukin (IL)-17, IL-6 and IL-1β in mouse model of arthritis by suppressing the Akt and Erk pathways ( 126 ).…”

Section: Repurposing Studiesmentioning

confidence: 99%

The Akt pathway in oncology therapy and beyond (Review)

et al. 2018

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Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt-regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side-effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.

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Section: Repurposing Studiesmentioning

confidence: 99%

The Akt pathway in oncology therapy and beyond (Review)

et al. 2018

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“…Dasatinib shares similar targets with imatinib and nilotinib, but dasatinib is more potent than imatinib and nilotinib at inhibiting tyrosine kinases (13). Dasatinib exhibits its own specific targets, such as PI3K and ERK (14), which are potent targets in RA treatment (15, 16). However, the effect of dasatinib on CIA is not known.…”

Section: Introductionmentioning

confidence: 99%

Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmune Arthritis

Guo

Yang

et al. 2019

Front. Immunol.

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Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1β, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis.

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“…When considering antidepressive treatment, direct effects of different antidepressant and neuroleptic medications definitely have to be taken into account. Quetiapine has complex anti-inflammatory effects on different cytokines, among these also IL-17, as shown repeatedly in a mouse model of collagen-induced arthritis (Kim et al, 2012;Pan et al, 2018). In addition, olanzapine and aripiprazole can reveal anti-inflammatory effects, and however, their impact on IL-17 has not yet firmly been investigated (Stapel et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The cytokine IL‐17A as a marker of treatment resistance in major depressive disorder?

Milenkovic

Sarubin

Hilbert

et al. 2019

Eur J of Neuroscience

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Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of the AKT and ERK signaling pathways

Abstract: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.

Cited by 13 publications

References 46 publications

The Akt pathway in oncology therapy and beyond (Review)

The Akt pathway in oncology therapy and beyond (Review)

Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmune Arthritis

The cytokine IL‐17A as a marker of treatment resistance in major depressive disorder?

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