Regulation by glycogen synthase kinase-3 of inflammation and T cells in CNS diseases.
Regulation by glycogen synthase kinase-3 of inflammation and T cells in CNS diseases.
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DOI：
10.3389/fnmol.2011.00018
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发表时间：
2011
影响因子：
4.8
通讯作者：
Beurel E
中科院分区：
文献类型：
--
作者：
Beurel E
已经发现神经炎症的升高的标志物与许多精神和神经退行性疾病相关，例如情绪障碍、阿尔茨海默病和多发性硬化症（MS）。由于神经炎症被认为有助于这些疾病的病理生理学，并损害对治疗干预和恢复的反应，因此重要的是要确定调节神经炎症的机制和控制神经炎症的潜在靶点。最近的研究结果表明，糖原合成酶激酶-3（GSK 3）是先天性和适应性免疫系统对炎症的重要调节因子。先天免疫系统的研究表明，GSK 3的抑制剂深刻地改变了由外周细胞和中央细胞产生的细胞因子的库，减少促炎细胞因子，并增加抗炎细胞因子。此外，GSK 3的抑制剂促进对炎性刺激的耐受性，减少反复暴露后的炎性细胞因子产生。对适应性免疫系统的研究表明，GSK 3调节T细胞产生细胞因子和T细胞分化为亚型，特别是Th 17细胞。GSK 3对转录因子的调节似乎在其免疫应答的调节中发挥重要作用，包括NF-κB、环AMP反应元件结合蛋白以及信号转导和转录激活因子-3。体内研究表明，GSK 3抑制剂改善外周和中枢炎症性疾病的临床症状，特别是实验性自身免疫性脑脊髓炎，MS的动物模型。因此，GSK 3抑制剂的开发和应用可能提供一种新的治疗策略，以减少与许多中枢神经系统疾病相关的神经炎症。
Elevated markers of neuroinflammation have been found to be associated with many psychiatric and neurodegenerative diseases, such as mood disorders, Alzheimer’s disease, and multiple sclerosis (MS). Since neuroinflammation is thought to contribute to the pathophysiology of these diseases and to impair responses to therapeutic interventions and recovery, it is important to identify mechanisms that regulate neuroinflammation and potential targets for controlling neuroinflammation. Recent findings have demonstrated that glycogen synthase kinase-3 (GSK3) is an important regulator of both the innate and adaptive immune systems’ contributions to inflammation. Studies of the innate immune system have shown that inhibitors of GSK3 profoundly alter the repertoire of cytokines that are produced both by peripheral and central cells, reducing pro-inflammatory cytokines, and increasing anti-inflammatory cytokines. Furthermore, inhibitors of GSK3 promote tolerance to inflammatory stimuli, reducing inflammatory cytokine production upon repeated exposure. Studies of the adaptive immune system have shown that GSK3 regulates the production of cytokines by T cells and the differentiation of T cells to subtypes, particularly Th17 cells. Regulation of transcription factors by GSK3 appears to play a prominent role in its regulation of immune responses, including of NF-κB, cyclic AMP response element binding protein, and signal transducer and activator of transcription-3. In vivo studies have shown that GSK3 inhibitors ameliorate clinical symptoms of both peripheral and central inflammatory diseases, particularly experimental autoimmune encephalomyelitis, the animal model of MS. Therefore, the development and application of GSK3 inhibitors may provide a new therapeutic strategy to reduce neuroinflammation associated with many central nervous system diseases.
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DOI：
10.1084/jem.185.9.1573
发表时间：
1997-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cope AP;Liblau RS;Yang XD;Congia M;Laudanna C;Schreiber RD;Probert L;Kollias G;McDevitt HO
通讯作者：
McDevitt HO
影响因子：
3.3
作者：
Beurel, E.;Jope, R. S.
通讯作者：
Jope, R. S.
影响因子：
6.4
作者：
Antoniv, Taras T.;Ivashkiv, Lionel B.
通讯作者：
Ivashkiv, Lionel B.
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
影响因子：
4.8
作者：
Chen, G;Bower, KA;Luo, J
通讯作者：
Luo, J