文章基本信息

标题：Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway
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作者：Yuxin Li ; Wuyang Yang ; Alfredo Quinones-Hinojosa 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep38247
语种：English
出版社：Springer Nature
摘要：Excessive microglial cells activation in response to inflammatory stimuli leads to synaptic loss, dysfunction, and neuronal cell death. Activated microglia are involved in the pathogenesis of neurological conditions and frequently contribute to several complications. Accumulating evidence suggests that signaling through PAR-1 is involved in inflammation, however, its function has yet to be fully elucidated. Here, we have demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1β, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells. In addition, we found that a PAR-1 antagonist, SCH, prevented LPS-induced excessive microglial activation in a dose-dependent manner. As a result of SCH treatment, neuronal cell death via up-regulation of Akt-mediated pathways was reduced. Our results demonstrate that the beneficial effects of SCH are linked to its ability to block an inflammatory response. Further, we found that SCH inhibited the death of PC12 neurons from the cytotoxicity of activated BV2 cells via activation of the PI3K/Akt pathway. These neuro-protective effects appear to be related to inhibition of PAR-1, and represents a novel neuroprotective strategy that could has potential for use in therapeutic interventions of neuroinflammatory disease.