Function of COX-2 and prostaglandins in neurological disease
Function of COX-2 and prostaglandins in neurological disease
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DOI：
10.1007/s12031-007-0058-8
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Andreasson, K.
中科院分区：
文献类型：
--
作者：
Liang, X.;Wu, L.;Andreasson, K.
诱导考克斯-2表达和酶活性促进了许多神经系统疾病模型中的神经元损伤。考克斯-2活性的抑制，无论是遗传性的还是非遗传性的，在中风、帕金森氏病和肌萎缩侧索硬化的啮齿动物模型中显示出神经保护作用。用非甾体抗炎药（NSAID）抑制考克斯活性可减少家族性阿尔茨海默病的鼠转基因模型中的炎症和淀粉样蛋白积累，并且NSAID的使用可降低健康老年人群中发展阿尔茨海默病的风险。COX介导的神经元损伤被认为是由于一种或多种前列腺素产物的下游效应，包括PGE（2）、PGD（2）、PGF（2 α）、PGI（2）（前列腺素）和TXA（2）（血栓素），其通过激活特定的前列腺素受体亚型和第二信使系统来影响细胞变化。在这个过程中，我们回顾了最近的数据表明前列腺素信号对神经元活力的影响，是矛盾的保护，当采取的背景下，考克斯-2诱导神经元损伤的兴奋性毒性的设置。相反，在炎症刺激的情况下，EP 2受体增强神经元损伤。这些研究结果表明，前列腺素在神经系统疾病中的反应具有额外的复杂性。
Induction of COX-2 expression and enzymatic activity promotes neuronal injury in a number of models of neurological disease. Inhibition of COX-2 activity, either genetically or pharmacologically, has been shown to be neuroprotective in rodent models of stroke, Parkinson's disease, and amyotrophic lateral sclerosis. Inhibition of COX activity with nonsteroidal anti-inflammatory drugs (NSAIDs) reduces inflammation and amyloid accumulation in murine transgenic models of Familial Alzheimer's disease, and the use of NSAIDs decreases the risk of developing Alzheimer's disease in healthy aging populations. COX-mediated neuronal injury is presumed be due to downstream effects of one or more prostaglandin products including PGE(2), PGD(2), PGF(2 alpha), PGI(2) (prostacylin) and TXA(2) (thromboxane) that effect cellular changes through activation of specific prostaglandin receptor subtypes and second messenger systems. In this proceeding, we review recent data demonstrating effects of prostaglandin signaling on neuronal viability that are paradoxically protective, when taken in the context that COX-2 induces neuronal injury in the setting of excitotoxicity. Conversely, in the context of an inflammatory stimulus, the EP2 receptor enhances neuronal injury. These findings argue for an additional level of complexity in the prostaglandin response in neurological disease.