TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB

Alzheimer's disease (AD) poses a significant threat to human life and health. The intraneuronal accumulation of beta-amyloid (A beta) plaques in the brains of AD patients results in neuronal cell death, which is a key factor that triggers multiple changes in the pathogenesis of AD. The inhibition of A beta-induced neuronal cell death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor alpha-induced protein 1 (TNFAIP1) is induced by and promotes A beta(25-35)-induced neurotoxicity in mouse neuronal cells, but the roles and regulatory mechanisms of TNFAIP1 are still largely unknown. In this study, our experimental results show that TNFAIP1 and p-TNFAIP1 (phosphorylation of TNFAIP1 at Ser280) are overexpressed in the neurons of the cortex and hippocampus in the brains of APP/PS1 mice, and the transcription factor NF-kappa B is involved in the A beta-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the A beta-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential ( increment psi m), and neuronal cell death in human SH-SY5Y cells. We further revealed that A beta increases the binding of TNFAIP1 to RhoB, and knockdown of RhoB attenuates the TNFAIP1-induced apoptosis of human SH-SY5Y cells. These data suggest that TNFAIP1 is closely associated with AD pathogenesis, and overexpression of TNFAIP1 in the neurons of the brains of AD patients plays a role in apoptosis, at least in part, via RhoB signaling.

Automated summary

This study reveals that TNFAIP1 is overexpressed in the neurons of AD mice, and it plays a role in Aβ-induced apoptosis through the RhoB signaling pathway, leading to increased ROS production and decreased mitochondrial membrane potential.