TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study.

Long Chen, Lu Wang, Gui-Feng Zhou, Yue Liu, Xue Chen, Xiao-Yong Xie, Qi-Xin Wen, Chen-Lu Li, Jie Yang, Guo-Jun Chen

Neuroscience letters 2023 Jun 21

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TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of β-secretase (BACE1) and C99, as well as Aβ peptides (including Aβ40 and Aβ42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1. Copyright © 2023. Published by Elsevier B.V.

Citation

Long Chen, Lu Wang, Gui-Feng Zhou, Yue Liu, Xue Chen, Xiao-Yong Xie, Qi-Xin Wen, Chen-Lu Li, Jie Yang, Guo-Jun Chen. TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study. Neuroscience letters. 2023 Jun 21;808:137265