Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine

Yao, Wei; Cao, Qianqian; Luo, Shilin; He, Lujuan; Yang, Chun; Chen, Jiaxu; Qi, Qi; Hashimoto, Kenji; Zhang, Ji-Chun

doi:10.1038/s41380-021-01377-7

Cited by 114 publications

(60 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nucleic acid-based therapeutics represent a promising technology platform to manipulate gene targets. Previously reported a new nucleic acid drug named cholesterol conjugated DNA/RNA heteroduplex oligonucleotide (HDO) [27]. The HDO carried cholesterol leading to ASO accumulation in the liver and was more potent at reducing the expression of target mRNA in the liver.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin

Gao

Chu

Xiao

et al. 2022

Preprint

View full text Add to dashboard Cite

Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy with limited therapeutic options. Metastasis is one of the main contributors to ICC progression and poor prognosis. However, the underlying mechanism of ICC metastasis remains largely unknown. Here, we showed that TANK-binding kinase 1 (TBK1), a serine/threonine-protein kinase, was significantly upregulated in tumor tissues of ICC patients with larger tumor diameter, lymph node metastasis, and advanced TNM stage. Consistently, during the different stages of cholangiocarcinoma (CCA) carcinogenesis (hyperplasia, dysplasia, and CCA), TBK1 showed a dynamic increase in spontaneous rat and mouse models. Functional studies showed that enforced expression of TBK1 promoted metastasis both in vitro and in vivo. Mechanistically, TBK1 directly interacts with β-catenin and stimulates its nuclear translocation, further activating the β-catenin-mediated epithelial-mesenchymal transition (EMT) process. Moreover, we demonstrate that the S172 site of TBK1 kinase domain was essential for the interaction between TBK1 and β-catenin as well as for TBK1 mediated β-catenin activation. In addition, high levels of TBK1 in clinical ICC tissues were correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. A TBK1 inhibitor GSK-8612 and the liver-specific accumulation of DNA/RNA heteroduplex oligonucleotide (TBK1-HDO) significantly reduced TBK1 expression of ICC and inhibited its intrahepatic metastasis. In summary, our study demonstrated that TBK1 could activate β-catenin via protein-protein interaction, then promote EMT and ICC metastasis, which might serve as a potential therapeutic target for patients with cholangiocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

“…7A). Notably, the HDO carried cholesterol leading to ASO accumulation in the liver and was more potent at reducing the expression of TBK1 mRNA in the liver [27,28] (Fig. 7B).…”

Section: Tbk1-hdo and Pharmacological Inhibition Of Tbk1 Reduce Cca C...mentioning

confidence: 99%

Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin

Gao

Chu

Xiao

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…More importantly, especially in the context of this review, MeCP2 S421 phosphorylation can be induced by early life stress in neurons of the parvocellular hypothalamic PVN [ 94 ], the previously described center of stress regulation. Moreover, antidepressant drugs such as imipramine, fluoxetine, or ketamine can induce S421 phosphorylation and reverse stress-induced depression, which will be discussed in the next section of this review [ 95 , 96 , 97 ].…”

Section: Mecp2 and Synaptic Plasticitymentioning

confidence: 99%

“…Finally, a recent study using a chronic social defeat stress model reported that the fast-acting antidepressant effects of (R)-ketamine, the enantiomer of the FDA-approved antidepressant (S)-ketamine, was mediated by the increased BDNF transcription. Such an increase resulted from the activation of CREB and MeCP2 suppression in microglia [ 97 ].…”

Section: Mecp2 and Stress-related Pathology: Focus On Depressionmentioning

confidence: 99%

The Role of MeCP2 in Regulating Synaptic Plasticity in the Context of Stress and Depression

Sánchez-Lafuente

Kalynchuk

Caruncho

et al. 2022

Cells

View full text Add to dashboard Cite

Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator that is highly abundant in the brain. It binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. MeCP2 has mainly been studied for its role in neurodevelopmental disorders, but alterations in MeCP2 are also present in stress-related disorders such as major depression. Impairments in both stress regulation and synaptic plasticity are associated with depression, but the specific mechanisms underlying these changes have not been identified. Here, we review the interplay between stress, synaptic plasticity, and MeCP2. We focus our attention on the transcriptional regulation of important neuronal plasticity genes such as BDNF and reelin (RELN). Moreover, we provide evidence from recent studies showing a link between chronic stress-induced depressive symptoms and dysregulation of MeCP2 expression, underscoring the role of this protein in stress-related pathology. We conclude that MeCP2 is a promising target for the development of novel, more efficacious therapeutics for the treatment of stress-related disorders such as depression.

show abstract

“…It is also a key target of antidepressants and serves to transduce their molecular signaling actions (Barbiero et al, 2007 ; Adaikkan et al, 2018 ). In partnership with CaMKIV, it can regulate CREB, a transcription factor of major interest in antidepressant activity (Blendy, 2006 ; Yao et al, 2021 ). Activation of CREB would result in increased BDNF transcription and further amplify the cascade.…”

Section: Reviewmentioning

confidence: 99%

Antidepressant-like effects of trophic factor receptor signaling

Sathyanesan

Newton

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

A significant body of research has demonstrated that antidepressants regulate neurotrophic factors and that neurotrophins themselves are capable of independently producing antidepressant-like effects. While brain derived neurotrophic factor (BDNF) remains the best studied molecule in this context, there are several structurally diverse trophic factors that have shown comparable behavioral effects, including basic fibroblast growth factor (FGF-2), insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF). In this review we discuss the structural and biochemical signaling aspects of these neurotrophic factors with antidepressant activity. We also include a discussion on a cytokine molecule erythropoietin (EPO), widely known and prescribed as a hormone to treat anemia but has recently been shown to function as a neurotrophic factor in the central nervous system (CNS).

show abstract

Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine

Cited by 114 publications

References 80 publications

Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin

Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin

The Role of MeCP2 in Regulating Synaptic Plasticity in the Context of Stress and Depression

Antidepressant-like effects of trophic factor receptor signaling

Contact Info

Product

Resources

About