TNIP2 通过调节 BACE1 的 3'UTR 抑制淀粉样蛋白形成：一项体外研究。
TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study.
机构信息
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China.
Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, 81 Bayi Road, Wenjiang District, Sichuan Province 611135, China.
出版信息
Neurosci Lett. 2023 Jun 21;808:137265. doi: 10.1016/j.neulet.2023.137265. Epub 2023 Apr 19.
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.
肿瘤坏死因子-α 诱导蛋白 3 相互作用蛋白 2（TNIP2）是 NF-κB 信号的负调节剂，可抑制炎症反应和细胞凋亡，并参与 RNA 代谢。在这项研究中，我们研究了 TNIP2 在与阿尔茨海默病（AD）密切相关的淀粉样蛋白形成中的潜在作用。我们发现 AD 的小鼠模型和细胞模型中 TNIP2 蛋白水平显著下降。在稳定表达全长人 APP695 的 SH-SY5Y 和 HEK 细胞（SY5Y-APP 和 HEK-APP）中，TNIP2 过表达降低了 β-分泌酶（BACE1）和 C99 的蛋白水平，以及 Aβ 肽（包括 Aβ40 和 Aβ42），而 α-分泌酶（ADAM10）和相关的 C83 则保持不变。我们进一步发现，TNIP2 促进了 BACE1 mRNA 的降解，并且能够与降低的荧光素酶活性结合到 3'非翻译区（3'UTR）。这些结果表明，TNIP2 通过调节 BACE1 的 3'UTR 相关 mRNA 衰减，有效地抑制了淀粉样蛋白形成。
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