NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation.

Abstract

NLRC3 inhibits inflammatory responses. Neuroinflammation induces and accelerates the onset of Alzheimer's disease (AD). This study is aimed at investigating whether NLRC3 plays a role in neuroinflammation, Aβ accumulation, and neuroprotection in AD mice. 12-month-old APP/PS1 transgenic and C57 mice were used for studies in vivo. In vitro, organotypic hippocampal slices were cultured. We found that the expression of NLRC3 was downregulated in the brain tissues of APP/PS1 mice. Mice in the APP/PS1 group had a significant attenuation of learning and memory ability compared to the control group, and the ability was improved in APP/PS1 + LV-NLRC3 mice. The expressions of 6E10, GFAP, Iba1, and PI3K in the hippocampus and brains of APP/PS1 mice were significantly higher than those of the control group, while the expressions of NeuN were lower than that of the control group. With the overexpression of NLRC3 in the APP/PS1 + LV-NLRC3 group, the expressions of 6e10, GFAP, Iba1, and PI3K were significantly lower, while the expression of NeuN was significantly higher compared to the APP/PS1 group. NLRC3 colocalized with NeuN. PI3K activation with 740YP increased the expression of GFAP and Iba-1 in the hippocampus with the exogenous NLRC3 protein. We conclude that NLRC3 may play an important role in the development and progression of AD. Downregulation of NLRC3 can lead to the activation of PI3K, resulting in abnormal plaque deposition, glial cell activation, and neuron loss during AD. NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation.