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

• Published in: Journal of molecular neuroscience Vol. 71; no. 6; pp. 1221 - 1233
• Main Authors: Xiao, Ye, Li, Yadan, Zhang, Huihui, Yang, Liping, Jiang, Yinghua, Wei, Chenxi, Feng, Xing, Xun, Yu, Yuan, Shishan, Xiang, Shuanglin, Liu, Ning
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2021; Springer Nature B.V
• Subjects: Alzheimer's disease; Apoptosis; Binding; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell death; Membrane potential; Mitochondria; Mortality; Neurochemistry; Neurodegenerative diseases; Neurology; Neurons; Neurosciences; Neurotoxicity; NF-κB protein; Pathogenesis; Phosphorylation; Presenilin 1; Proteomics; Reactive oxygen species; Regulatory mechanisms (biology); Senile plaques; Tumor necrosis factor-α; β-Amyloid; Aβ; TNFAIP1; Alzheimer’s disease; SH-SY5Y cells; RhoB
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01748-9

Alzheimer’s disease (AD) poses a significant threat to human life and health. The intraneuronal accumulation of β-amyloid (Aβ) 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 Aβ-induced neuronal cell death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor α-induced protein 1 (TNFAIP1) is induced by and promotes Aβ 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-κB is involved in the Aβ-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the Aβ-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (∆Ψm), and neuronal cell death in human SH-SY5Y cells. We further revealed that Aβ 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.