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排序方式: 共有2642条查询结果,搜索用时 15 毫秒
91.
Xiaohong Zhang Xuezhen Zhu Xiaoyang Bi Jiguang Huang Lijuan Zhou 《International journal of molecular sciences》2022,23(14)
The insulin receptor (IR) is a transmembrane protein that is activated by ligands in insulin signaling pathways. The IR has been considered as a novel therapeutic target for clinical intervention, considering the overexpression of its protein and A-isoform in multiple cancers, Alzheimer’s disease, and Type 2 diabetes mellitus in humans. Meanwhile, it may also serve as a potential target in pest management due to its multiple physiological influences in insects. In this review, we provide an overview of the structural and molecular biology of the IR, functions of IRs in humans and insects, physiological and nonpeptide small molecule modulators of the IR, and the regulating mechanisms of the IR. Xenobiotic compounds and the corresponding insecticidal chemicals functioning on the IR are also discussed. This review is expected to provide useful information for a better understanding of human IR-related diseases, as well as to facilitate the development of novel small-molecule activators and inhibitors of the IR for use as medicines or pesticides. 相似文献
92.
M3受体是人体内分布广泛的一种重要的毒蕈碱乙酰胆碱受体亚型,与膀胱过度活动症、心律失常、呼吸道及支气管疾病密切相关.设计与合成M3受体拮抗剂对于开发治疗相关疾病的药物具有重要理论意义和应用价值。本文采用同源模建方法,构建了人M3受体蛋白的三维结构,基于M3受体拮抗剂的结构构建了其药效团模型,其中较理想的模型含有6个药效团特征元素。利用药效团模型进行了虚拟筛选,虚拟筛选的数据库是本实验室构建的虚拟化合物库,发现了10个新型的对M3受体有拮抗作用的化合物。最后对这10个化合物进行了分子对接,根据对接结果,发现3个化合物对接能量及结合方式比较合理,为M3受体拮抗剂的合成研究及活性测定奠定了基础。 相似文献
93.
Dina Kata Ilona Grf Zsfia Hoyk Eszter Ducza Mria A. Deli Istvn Zupk Imre Fldesi 《International journal of molecular sciences》2022,23(16)
Estrogens regulate a variety of neuroendocrine, reproductive and also non-reproductive brain functions. Estradiol biosynthesis in the central nervous system (CNS) is catalyzed by the enzyme aromatase, which is expressed in several brain regions by neurons, astrocytes and microglia. In this study, we performed a complex fluorescent immunocytochemical analysis which revealed that aromatase is colocalized with the nuclear stain in glial fibrillary acidic protein (GFAP) positive astrocytes in cell cultures. Confocal immunofluorescent Z-stack scanning analysis confirmed the colocalization of aromatase with the nuclear DAPI signal. Nuclear aromatase was also detectable in the S100β positive astrocyte subpopulation. When the nuclear aromatase signal was present, estrogen receptor alpha was also abundant in the nucleus. Immunostaining of frozen brain tissue sections showed that the nuclear colocalization of the enzyme in GFAP-positive astrocytes is also detectable in the adult rat brain. CD11b/c labelled microglial cells express aromatase, but the immunopositive signal was distributed only in the cytoplasm both in the ramified and amoeboid microglial forms. Immunostaining of rat ovarian tissue sections and human granulosa cells revealed that aromatase was present only in the cytoplasm. This novel observation suggests a new unique mechanism in astrocytes that may regulate certain CNS functions via estradiol production. 相似文献
94.
Keren Nitzan Leah Ellenbogen Ziv Bentulila Dekel David Motty Franko Emanuela P. Break Michal Zoharetz Alon Shamir Yosef Sarne Ravid Doron 《International journal of molecular sciences》2022,23(16)
Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus. We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC. The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset. 相似文献
95.
Sighild Lemarchant Mlissa Sourioux Juliette Le Douce Alexandre Henriques Noëlle Callizot Sandrine Hugues Mlissa Farinelli Yann Godfrin 《International journal of molecular sciences》2022,23(16)
NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions. 相似文献
96.
基于序列的G蛋白偶联受体-药物相互作用预测研究 总被引:1,自引:0,他引:1
准确预测G蛋白质偶联受体(GPCR)是否与药物(Drug)相互作用是新药开发的关键步骤之一。从时间和费用方面来说,通过生物实验的方法来确定GPCR-Drug是否相互作用的代价是昂贵的。因此,直接从蛋白质序列出发预测GPCR-Drug的相互作用具有重要的意义。提出了一种基于序列的GPCR-Drug相互作用预测方法:从蛋白质序列抽取进化信息特征;对药物抽取指纹特征;基于上述两种特征,使用基于证据理论的K近邻算法进行分类预测。在标准数据集上的实验结果表明了所述方法的有效性。 相似文献
97.
在计算神经科学领域,大规模神经元网络的并行仿真对探索和揭示生物大脑中信息传递机制有着重要作用。为加速大规模神经元网络仿真,提出一种模块独立性强、耦合度低的基于突触递质-受体离子通道动力学的神经元网络的并行算法。通过分析化学突触信息传递机理及递质分子、受体离子通道动力学特征,提出了递质-受体计算分离的思想,增强了突触前神经元引起的递质分子浓度计算与突触后绑定状态的受体浓度计算之间的独立性,降低突触电流计算中突触前神经元状态和突触后神经元状态之间的耦合度。基于上述思想,设计并实现了一种生物神经网络并行算法。仿真结果表明了该算法的高效性。 相似文献
98.
Dong-Yong Hong Dong-Hun Lee Ji-Young Lee Eun-Chae Lee Sang-Won Park Man-Ryul Lee Jae-Sang Oh 《International journal of molecular sciences》2022,23(15)
The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood–brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (Aβ) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits. 相似文献
99.
As the most recent melanocortin receptor (MCR) identified, melanocortin-5 receptor (MC5R) has unique tissue expression patterns, pharmacological properties, and physiological functions. Different from the other four MCR subtypes, MC5R is widely distributed in both the central nervous system and peripheral tissues and is associated with multiple functions. MC5R in sebaceous and preputial glands regulates lipid production and sexual behavior, respectively. MC5R expressed in immune cells is involved in immunomodulation. Among the five MCRs, MC5R is the predominant subtype expressed in skeletal muscle and white adipose tissue, tissues critical for energy metabolism. Activated MC5R triggers lipid mobilization in adipocytes and glucose uptake in skeletal muscle. Therefore, MC5R is a potential target for treating patients with obesity and diabetes mellitus. Melanocortin-2 receptor accessory proteins can modulate the cell surface expression, dimerization, and pharmacology of MC5R. This minireview summarizes the molecular and pharmacological properties of MC5R and highlights the progress made on MC5R in energy metabolism. We poInt. out knowledge gaps that need to be explored in the future. 相似文献
100.
果蔬鲜切后会产生伤乙烯,加快果蔬的后熟和衰老。本文以野生型(Wide-type,Wt型)和乙烯受体Le ETR-3缺失型(Never-ripe,Nr突变型)两个品种绿熟期番茄为实验材料,鲜切处理后于4℃贮藏,并在贮藏期间测定了番茄生理品质指标。结果表明:与Wt型番茄相比,Nr突变型番茄果皮亮度变暗和颜色转红发生推迟,呼吸强度明显降低,失重损失减小,硬度下降延缓,可溶性固形物、可溶性糖、可滴定酸和VC含量下降缓慢,表明在贮藏期间Nr突变型番茄贮藏品质能够较好的得到保持。 相似文献