Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Zheng, Jin; Suo, Lun; Zhou, Yuxiao; Jia, Liling; Li, Jingwei; Kuang, Yanping; Cui, Donghong; Zhang, Xuehong; Wu, Qiang

doi:10.1093/jmcb/mjab057

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…Previous studies have found that Npas4, an immediate early gene, is enhanced in Pyk2 knockout mice, but how it Mediators of Inflammation is regulated and its molecular mechanisms remain unclear [84]. Inhibition of Fyn can reduce the expression of inflammatory factors and upregulate the expression of Npas4, which is regulated by Pyk2.…”

Section: Inflammation and Fynmentioning

confidence: 99%

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Tang

et al. 2022

Mediators of Inflammation

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Ischemic stroke caused by arterial occlusion is the most common type of stroke and is one of the leading causes of disability and death, with the incidence increasing each year. Fyn is a nonreceptor tyrosine kinase belonging to the Src family of kinases (SFKs), which is related to many normal and pathological processes of the nervous system, including neurodevelopment and disease progression. In recent years, more and more evidence suggests that Fyn may be closely related to cerebral ischemia-reperfusion, including energy metabolism disorders, excitatory neurotoxicity, intracellular calcium homeostasis, free radical production, and the activation of apoptotic genes. This paper reviews the role of Fyn in the pathological process of cerebral ischemia-reperfusion, including neuroexcitotoxicity and neuroinflammation, to explore how Fyn affects specific signal cascades and leads to cerebral ischemia-reperfusion injury. In addition, Fyn also promotes the production of superoxide and endogenous NO, so as to quickly react to produce peroxynitrite, which may also mediate cerebral ischemia-reperfusion injury, which is discussed in this paper. Finally, we revealed the treatment methods related to Fyn inhibitors and discussed its potential as a clinical treatment for ischemic stroke.

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Section: Inflammation and Fynmentioning

confidence: 99%

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Tang

et al. 2022

Mediators of Inflammation

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“…Gene editing techniques, acting as a potential therapeutic option, have been widely investigated in treatment of the nuclear genetic diseases over the past decade ( Sharma et al, 2015 ; Nelson et al, 2016 ; De Ravin et al, 2017 ; Zheng et al, 2022 ), with an increasing number of clinical trials ongoing ( Arabi et al, 2022 ). However, its implication in mitochondrial diseases caused by mtDNA mutations has been hampered by the lack of efficient tools to manipulate the mtDNA ( Silva-Pinheiro and Minczuk, 2022 ), with the exception that deleterious mtDNA copies could be cut and eliminated by Zinc finger-fused ( Minczuk et al, 2008 ; Gammage et al, 2014 ; Gammage et al, 2016a ; Gammage et al, 2016b ; Gammage et al, 2018b ) or TALE-fused fokI nuclease ( Bacman et al, 2013 ; Reddy et al, 2015 ; Bacman et al, 2018 ; Pereira et al, 2018 ; Yang et al, 2018 ), as well as the monomeric enzyme based on the TALE system ( Pereira et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner

Qiu,

Wu,

Xie

et al. 2024

Front. Bioeng. Biotechnol.

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Introduction: Mitochondrial diseases caused by mtDNA have no effective cures. Recently developed DddA-derived cytosine base editors (DdCBEs) have potential therapeutic implications in rescuing the mtDNA mutations. However, the performance of DdCBEs relies on designing different targets or improving combinations of split-DddA halves and orientations, lacking knowledge of predicting the results before its application.Methods: A series of DdCBE pairs for wide ranges of aC or tC targets was constructed, and transfected into Neuro-2a cells. The mutation rate of targets was compared to figure out the potential editing rules.Results: It is found that DdCBEs mediated mtDNA editing is predictable: 1) aC targets have a concentrated editing window for mtDNA editing in comparison with tC targets, which at 5’C8-11 (G1333) and 5’C10-13 (G1397) for aC target, while 5’C4-13 (G1333) and 5’C5-14 (G1397) for tC target with 16bp spacer. 2) G1333 mediated C>T conversion at aC targets in DddA-half-specific manner, while G1333 and G1397 mediated C>T conversion are DddA-half-prefer separately for tC and aC targets. 3) The nucleotide adjacent to the 3’ end of aC motif affects mtDNA editing. Finally, by the guidance of these rules, a cell model harboring a pathogenic mtDNA mutation was constructed with high efficiency and no bystander effects.Discussion: In summary, this discovery helps us conceive the optimal strategy for accurate mtDNA editing, avoiding time- and effort-consuming optimized screening jobs.

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Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin‐releasing hormone neurons protects from obesity

Liu,

Lin,

Najam

et al. 2024

Obesity

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ObjectiveHere, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis.MethodsWe used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin‐releasing hormone (CRH) neurons and compared them with wild‐type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation.ResultsSimilar to global double‐knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline‐rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation.ConclusionsOur data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Cited by 4 publications

References 72 publications

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner

Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin‐releasing hormone neurons protects from obesity

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