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.

阿尔茨海默病 (AD) 对人类的生命和健康构成重大威胁。AD患者大脑中β-淀粉样蛋白（Aβ）斑块在神经元内的积累导致神经元细胞死亡，这是引发AD发病机制多重变化的关键因素。抑制 Aβ 诱导的神经元细胞死亡可能有助于 AD 的干预和治疗。我们先前的研究报道，肿瘤坏死因子α诱导的蛋白1（TNFAIP1）通过诱导并促进Aβ _25-35- 诱导小鼠神经元细胞的神经毒性，但 TNFAIP1 的作用和调节机制在很大程度上仍是未知的。在本研究中，我们的实验结果表明，APP/PS1 小鼠大脑皮层和海马神经元中 TNFAIP1 和 p-TNFAIP1（TNFAIP1 Ser280 磷酸化）过表达，转录因子 NF-κB 参与Aβ 诱导的 TNFAIP1 上调。此外，我们的结果表明 TNFAIP1 有助于 Aβ 诱导的活性氧 (ROS) 产生、线粒体膜电位 (ΔΨm) 降低和人 SH-SY5Y 细胞中的神经元细胞死亡。我们进一步揭示了 Aβ 增加了 TNFAIP1 与 RhoB 的结合，并且 RhoB 的敲低减弱了 TNFAIP1 诱导的人 SH-SY5Y 细胞凋亡。