Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation.
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation.
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DOI：
10.1186/s12974-021-02325-6
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发表时间：
2021-11-27
影响因子：
9.3
通讯作者：
Semple BD
中科院分区：
文献类型：
--
作者：
Chu E;Mychasiuk R;Hibbs ML;Semple BD
小胶质细胞是哺乳动物中枢神经系统内先天免疫的重要介质。典型的小胶质细胞反应是短暂的，旨在通过协调病原体和碎片的去除以及受损神经元的再生来恢复体内平衡。然而，长时间和持续的小胶质细胞活化可驱动慢性神经炎症，并与神经退行性疾病相关。最近的证据表明，涉及磷脂酰肌醇3-激酶（PI 3 K）和蛋白激酶B（AKT）的小胶质细胞信号通路的异常可能会导致小胶质细胞活性的改变和神经免疫反应的加剧。在这一范围审查中，PI 3 K-AKT信号在小胶质细胞中的已知和疑似作用，无论是在健康和病理状态下，将被检查，并在小胶质细胞中诱导PI 3 K-AKT信号的关键小胶质细胞受体将被描述。由于异常信号传导与神经退行性疾病的发病相关，因此还将探索适应不良的PI 3 K-AKT信号传导与神经退行性疾病发展之间的关系。最后，将重点介绍小胶质细胞PI 3 K-AKT信号转导被调节的研究，因为这可能被证明是未来治疗一系列神经炎症疾病的有前景的治疗方法。
Microglia are integral mediators of innate immunity within the mammalian central nervous system. Typical microglial responses are transient, intending to restore homeostasis by orchestrating the removal of pathogens and debris and the regeneration of damaged neurons. However, prolonged and persistent microglial activation can drive chronic neuroinflammation and is associated with neurodegenerative disease. Recent evidence has revealed that abnormalities in microglial signaling pathways involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) may contribute to altered microglial activity and exacerbated neuroimmune responses. In this scoping review, the known and suspected roles of PI3K-AKT signaling in microglia, both during health and pathological states, will be examined, and the key microglial receptors that induce PI3K-AKT signaling in microglia will be described. Since aberrant signaling is correlated with neurodegenerative disease onset, the relationship between maladapted PI3K-AKT signaling and the development of neurodegenerative disease will also be explored. Finally, studies in which microglial PI3K-AKT signaling has been modulated will be highlighted, as this may prove to be a promising therapeutic approach for the future treatment of a range of neuroinflammatory conditions.
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影响因子：
7.3
作者：
Amici SA;Dong J;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
16.8
作者：
Crotti A;Glass CK
通讯作者：
Glass CK
影响因子：
8.3
作者：
Baba, Tanefumi;Kameda, Masahiro;Date, Isao
通讯作者：
Date, Isao
影响因子：
5.6
作者：
Da Pozzo, Eleonora;Tremolanti, Chiara;Martini, Claudia
通讯作者：
Martini, Claudia
影响因子：
8.7
作者：
Barodia, Sandeep K.;McMeekin, Laura J.;Goldberg, Matthew S.
通讯作者：
Goldberg, Matthew S.