KL-FGF23-VD Axis in Improving Late-Onset Alzheimer's Disease by Modulating IKK/NF- κ B Signal Pathway

Materials and methods: LOAD rats and Aβ microglia were constructed by using Aβ 1-40 and IBO mixture. The effect of KL-FGF23-VD axis on LOAD was investigated by transfecting overexpressing and interfering with KL gene adenovirus, and IKK-16 was added to Aβ microglia to explore the effect of KL-FGF23-VD axis on regulation of IKK/NF-κB signaling pathway.

Results: The results showed that, in KL-OE group, FGF23 was decreased in the hippocampus of LOAD rats compared with control and KL-si, and the trend was opposite in the KL-si group. The KL-FGF23-VD axis can alleviate inflammatory response, reduce the deposition of Aβ, and inhibit activation of the NF-κB pathway and neuron apoptosis in brain tissue of LOAD rats. In Aβ microglia, the expression of KL-FGF23-VD axis was consistent with animal experiments. The KL-FGF23-VD axis can inhibit the expression of Aβ microglia inflammatory factors and the activation of microglia and NF-κB pathway. Meanwhile, IKK expression was decreased in KL-OE group compared with KL-si and Control. In the IKK-16 addition group, the ability of KL-FGF23-VD axis to inhibit the activation of microglia and NF-κB pathway was enhanced.

Conclusions: These findings suggest a potential role of the KL-FGF23-VD axis in AD treatment by regulating the IKK/NF-κB pathway.

Comments：

The study investigated the effect of the KL-FGF23-VD axis on LOAD using Aβ microglia and LOAD rats constructed using Aβ 1-40 and IBO mixture. The researchers transfected overexpressing and interfering with KL gene adenovirus and added IKK-16 to explore the effect of KL-FGF23-VD axis on the regulation of the IKK/NF-κB signaling pathway.

The results showed that the KL-FGF23-VD axis can alleviate the inflammatory response, reduce the deposition of Aβ, and inhibit the activation of the NF-κB pathway and neuron apoptosis in brain tissue of LOAD rats. In Aβ microglia, the KL-FGF23-VD axis can inhibit the expression of Aβ microglia inflammatory factors and the activation of microglia and NF-κB pathway. In addition, IKK expression was decreased in KL-OE group compared with KL-si and Control, and in the IKK-16 addition group, the ability of KL-FGF23-VD axis to inhibit the activation of microglia and NF-κB pathway was enhanced.

Overall, the study suggests that the KL-FGF23-VD axis may have potential therapeutic value for AD treatment by regulating the IKK/NF-κB pathway.

Related Products

Cat.No.	Product Name	Information
S2882	IKK-16	IKK-16 is a selective IκB kinase (IKK) inhibitor for IKK-2, IKK complex and IKK-1 with IC50 of 40 nM, 70 nM and 200 nM in cell-free assays, respectively. IKK-16 also inhibits LRRK2 Ser935 phosphorylation in cells and LRRK2 kinase activity in vitro with IC50 of 50 nM.

Related Targets

IκB/IKK LRRK2