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

- Aβ up-regulates the expression of TRPC6 via NFκB.
- TRPC6 inhibition reduces the Aβ-induced expression of cytokines and COX-2.
- TRPC6 knock-down protects the hippocampus neurons.
- COX-2 inhibition improves neuron survival.

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.