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 ?-amyloid (A?) 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?-induced neuronal cell ...
death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor ?-induced protein 1 (TNFAIP1) is induced by and promotes A?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-?B is involved in the A?-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the A?-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (??m), and neuronal cell death in human SH-SY5Y cells. We further revealed that A? 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Apoptosis, Brain, Cell Line, Tumor, Humans, Membrane Potential, Mitochondrial, Mice, NF-kappa B, Neurons, Presenilin-1, Protein Binding, Reactive Oxygen Species, Up-Regulation, rhoB GTP-Binding Protein
J Mol Neurosci
Date: Jun. 01, 2021
Download Curated Data For This Publication
234040
Switch View:
  • Interactions 1