Involvement of RhoA/ROCK Signaling in A-Induced Chemotaxis, Cytotoxicity and Inflammatory Response of Microglial BV2 Cells
Involvement of RhoA/ROCK Signaling in A-Induced Chemotaxis, Cytotoxicity and Inflammatory Response of Microglial BV2 Cells
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RhoA/ROCK 信号转导参与 A 诱导的小胶质细胞 BV2 细胞的趋化性、细胞毒性和炎症反应
DOI：
10.1007/s10571-019-00668-6
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发表时间：
2019
影响因子：
4
通讯作者：
Zhu Cuiqing
中科院分区：
文献类型：
--
作者：
Zhang Xiaoxu;Ye Piao;Wang D;an;Liu Yunsheng;Cao Lan;Wang Yancong;Xu Yuxia;Zhu Cuiqing
反应性小胶质细胞聚集在脑内淀粉样斑块周围是阿尔茨海默病（AD）的组织病理学特征，反映了神经炎症在AD发病机制中的作用。β-淀粉样肽（β-Amyloid peptide，A β）可诱导小胶质细胞产生趋化性、细胞毒性和炎症反应，但其作用机制尚不清楚。考虑到RhoA/ROCK信号在细胞迁移中的基本作用及其在AD和神经炎症中的广泛意义，我们假设RhoA/ROCK信号可能参与A β诱导的小胶质细胞反应。在小鼠体内模型中，我们观察到在APP/PS1转基因和A β立体定向注射的情况下，RhoA在反应性小胶质细胞中的表达水平升高。通过一系列体外细胞迁移、细胞毒性和生化实验，我们发现RhoA/ROCK信号通路在A β诱导的小胶质细胞BV2反应中起重要作用。小分子药物法舒地尔和Y27632显示出显著的有益效果，这意味着RhoA/ROCK信号传导抑制剂在AD治疗中的治疗潜力。
Reactive microglia clustering around amyloid plaques in brain is a histopathological feature of Alzheimer’s disease (AD) and reflects the contribution of neuroinflammation in AD pathogenesis. β-Amyloid peptide (Aβ) has been shown to induce a range of microglial responses including chemotaxis, cytotoxicity and inflammation, but the underlying mechanism is poorly understood. Considering the fundamental role of RhoA/ROCK signaling in cell migration and its broad implication in AD and neuroinflammation, we hypothesized that RhoA/ROCK signaling might be involved in Aβ-induced microglial responses. From in vivo mouse models including APP/PS1 transgene and fibrillar Aβ stereotactic injection, we observed the elevated expression level of RhoA in reactive microglia. Through a series in vitro cell migration, cytotoxicity and biochemistry assays, we found that RhoA/ROCK signaling plays an essential role in Aβ-induced responses of microglial BV2 cells. Small molecular agents Fasudil and Y27632 showed prominent beneficial effects, which implies the therapeutic potential of RhoA/ROCK signaling inhibitors in AD treatment.