NF-κB dependent up-regulation of TRPC6 by Aβ in BV-2 microglia cells increases COX-2 expression and contributes to hippocampus neuron damage

作者：Liu, Na; Zhuang, Yuansu; Zhou, Zhikui; Zhao, Jinhua; Chen, Qiaoyun; Zheng, Jinxu^*

来源：Neuroscience Letters, 2017, 651: 1-8.

DOI：10.1016/j.neulet.2017.04.056

• TRPC6
• A beta
• BV-2 microglia
• NF-kappa B
• COX-2
• Alzheimer's disease

The deposition of amyloid beta-protein (A beta) has been involved in neurodegeneration of Alzheimer's disease (AD). Besides A beta 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 A beta 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 A beta. A beta up regulates the level of TRPC6 via NF-kappa B in BV-2 microglia and increases the expression of pro inflammatory factors and oxidative enzyme, COX-2. Knock down of TRPC6 reduces the A beta 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 A beta induced inflammatory damage. Collectively, our studies suggest that A beta increase the expression of TRPC6 via NF-kappa B in BV-2 microglia and promotes the production of COX-2, which induces hippocampus neuron damage.

• 出版日期2017-6-9
• 单位江苏大学