Principles of inflammasome priming and inhibition: Implications for psychiatric disorders.
Principles of inflammasome priming and inhibition: Implications for psychiatric disorders.
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DOI：
10.1016/j.bbi.2018.06.010
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
Herman FJ;Pasinetti GM
由先天免疫系统产生的炎性蛋白是一个紧密协调的过程，使身体能够有效地应对外源性和内源性威胁。最近，越来越多的证据表明，炎症反应系统的紊乱不仅会引发自身免疫性疾病，还会对神经功能和心理健康产生有害影响。由于大脑中的炎症主要是由小胶质细胞介导的，因此人们越来越关注这些细胞启动和传播神经炎症的机制。小胶质细胞在最初识别到环境应激源后可以进入持续活跃的状态，此后容易在随后的应激源暴露后引发放大的和持续的炎症反应。最近，NLRP3炎症体成为人们关注的焦点，研究的焦点是为什么启动的小胶质细胞对环境侮辱敏感。它在先天免疫系统中的功能被调节，从而支持该复合体在调节神经炎性反应中的作用。小胶质细胞中NLRP3炎症体的激活导致酶原炎性白介素裂解成功能性形式，从而在局部神经元环境中引起一系列相应的影响。有证据支持这一原理，即在启动的神经免疫系统中，NLRP3激活阈值的降低会导致持续的神经炎症或炎性细胞因子的放大产生，如IL-1β和IL-18。在一个人的一生中，持续的神经炎症随后会导致定义心理障碍的病理生理特征。因此，以NLRP3炎症体复合体为靶点可能是限制精神障碍(如严重抑郁障碍)中神经炎性状态的一种创新和有效的方法。
The production of inflammatory proteins by the innate immune system is a tightly orchestrated procedure that allows the body to efficiently respond to exogenous and endogenous threats. Recently, accumulating evidence has indicated that disturbances in the inflammatory response system not only provoke autoimmune disorders, but also can have deleterious effects on neuronal function and mental health. As inflammation in the brain is primarily mediated by microglia, there has been an expanding focus on the mechanisms through which these cells initiate and propagate neuroinflammation. Microglia can enter persistently active states upon their initial recognition of an environmental stressor and are thereafter prone to elicit amplified and persistent inflammatory responses following subsequent exposures to stressors. A recent focus on why primed microglia cells are susceptible to environmental insults has been the NLRP3 inflammasome. Its function within the innate immune system is regulated in such a manner that supports a role for the complex in gating neuroinflammatory responses. The activation of NLRP3 inflammasome in microglia results in the cleavage of zymogen inflammatory interleukins into functional forms that elicit a number of consequential effects in the local neuronal environ ment. There is evidence to support the principle that within primed neuroimmune systems a lowered threshold for NLRP3 activation can cause persistent neuroinflammation or the amplified production of inflammatory cytokines, such as IL-1β and IL-18. Over the course of an individual’s lifetime, persistent neuroinflammation can subsequently lead to the pathophysiological signatures that define psychological disorders. Therefore, targeting the NLRP3 inflammasome complex may represent an innovative and consequential approach to limit neuroinflammatory states in psychiatric disorders, such as major depressive disorder.
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DOI：
10.1038/npp.2010.159
发表时间：
2010-12
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
24.1
作者：
通讯作者：
--
影响因子：
--
作者：
Arostegui, Juan I.;Lopez Saldana, Ma Dolores;Yaguee, Jordi
通讯作者：
Yaguee, Jordi
影响因子：
5.1
作者：
Alcocer-Gomez, Elisabet;Ulecia-Moron, Cristina;Cordero, Mario D.
通讯作者：
Cordero, Mario D.