TNIP2 inhibits amyloidogenesis by regulating the 3′UTR of BACE1: An in vitro study
TNIP2 inhibits amyloidogenesis by regulating the 3′UTR of BACE1: An in vitro study
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DOI：
10.1016/j.neulet.2023.137265
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发表时间：
2023-05-06
影响因子：
2.5
通讯作者：
Chen，Guo-Jun
中科院分区：
文献类型：
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作者：
Chen，Long;Wang，Lu;Chen，Guo-Jun
TNFAIP 3相互作用蛋白2（TNIP 2）是NF-κB信号负调控因子，参与RNA代谢，抑制炎症反应和细胞凋亡。在这项研究中，我们研究了TNIP 2在与阿尔茨海默病（AD）密切相关的淀粉样蛋白生成中的潜在作用。我们发现TNIP 2蛋白水平在AD的小鼠和细胞模型中均显著下降。在稳定表达人全长APP 695（SY 5 Y-APP和HEK-APP）的SH-SY 5 Y和HEK细胞中，TNIP 2过表达降低了β-分泌酶（BACE 1）和C99以及Aβ肽（包括Aβ40和Aβ42）的蛋白水平，而α-分泌酶（ADAM 10）和相关C83的蛋白水平保持不变。TNIP 2能促进BACE 1 mRNA的降解，并能与3′非翻译区结合，降低荧光素酶活性。这些结果表明TNIP 2通过调节BACE 1的3′ UTR相关mRNA衰减来有效抑制淀粉样蛋白形成过程。
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.