Liu Na, Zhuang Yuansu, Zhou Zhikui, Zhao Jinhua, Chen Qiaoyun, Zheng Jinxu
Department of Neurology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, China.
Department of Central Laboratory, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, China.
Neurosci Lett. 2017 Jun 9;651:1-8. doi: 10.1016/j.neulet.2017.04.056. Epub 2017 Apr 27.
The deposition of amyloid β-protein (Aβ) has been involved in neurodegeneration of Alzheimer's disease (AD). Besides Aβ plaques and neuronal loss, microglia activation is also common in AD patient brains, suggesting its important role in the pathogenesis of AD. Although activation of microglia by Aβ plaques has been demonstrated, the mechanism underlying it is still largely unclear. Here, we found that TRPC6 has a crucial role in microglia activation by Aβ. Aβ up-regulates the level of TRPC6 via NF-κB in BV-2 microglia and increases the expression of pro-inflammatory factors and oxidative enzyme, COX-2. Knock-down of TRPC6 reduces the Aβ-induced expression of pro-inflammatory factors and COX-2 and the damage of hippocampus neurons. Furthermore, inhibition of COX-2 also protects hippocampus neurons from Aβ-induced inflammatory damage. Collectively, our studies suggest that Aβ increase the expression of TRPC6 via NF-κB in BV-2 microglia and promotes the production of COX-2, which induces hippocampus neuron damage.
淀粉样β蛋白（Aβ）的沉积与阿尔茨海默病（AD）的神经退行性变有关。除了Aβ斑块和神经元丢失外，小胶质细胞激活在AD患者大脑中也很常见，这表明其在AD发病机制中起重要作用。尽管已证明Aβ斑块可激活小胶质细胞，但其潜在机制仍不清楚。在这里，我们发现TRPC6在Aβ激活小胶质细胞中起关键作用。Aβ通过NF-κB上调BV-2小胶质细胞中TRPC6的水平，并增加促炎因子和氧化酶COX-2的表达。敲低TRPC6可降低Aβ诱导的促炎因子和COX-2的表达以及海马神经元的损伤。此外，抑制COX-2也可保护海马神经元免受Aβ诱导的炎症损伤。总之，我们的研究表明，Aβ通过NF-κB增加BV-2小胶质细胞中TRPC6的表达，并促进COX-2的产生，从而诱导海马神经元损伤。
