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

作者全名："Chen, Long; Wang, Lu; Zhou, Gui-Feng; Liu, Yue; Chen, Xue; Xie, Xiao-Yong; Wen, Qi-Xin; Li, Chen-Lu; Yang, Jie; Chen, Guo-Jun"

作者地址："[Chen, Long; Wang, Lu; Zhou, Gui-Feng; Liu, Yue; Chen, Xue; Xie, Xiao-Yong; Wen, Qi-Xin; Li, Chen-Lu; Chen, Guo-Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Yang, Jie] Chengdu Univ TCM, Affiliated Sichuan Prov Rehabil Hosp, 81 Bayi Rd, Wenjiang Dist 611135, Sichuan, Peoples R China"

通信作者："Chen, GJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：NEUROSCIENCE LETTERS

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001005114200001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：808

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：TNIP2; BACE1; Amyloidogenesis; mRNA decay; 3 ' UTR; RBP

摘要："TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-kappa B 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 beta-secretase (BACE1) and C99, as well as A beta peptides (including A beta 40 and A beta 42), while those of alpha-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."

基金机构："NSFC [81971030, 82271461]; Chongqing Education commission [KJZD-K201900404]"

基金资助正文：Funding This work was supported by NSFC (81971030 and 82271461) and Chongqing Education commission (KJZD-K201900404) to G -J Chen.