DEAD-Box Helicase 17 Promotes Amyloidogenesis by Regulating BACE1 Translation

作者全名："Liu, Yue; Zhou, Guifeng; Song, Li; Wen, Qixin; Xie, Shiqi; Chen, Long; Wang, Lu; Xie, Xiaoyong; Chen, Xue; Pu, Yalan; Chen, Guojun"

作者地址："[Liu, Yue; Zhou, Guifeng; Song, Li; Wen, Qixin; Xie, Shiqi; Chen, Long; Wang, Lu; Xie, Xiaoyong; Chen, Xue; Pu, Yalan; Chen, Guojun] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

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

来源：BRAIN SCIENCES

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000995583700001

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：13

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：DDX17; amyloidogenesis; BACE1; Alzheimer's disease; RNA helicase; APP; beta-amyloid; protein; translation; 5 ' UTR; RBP

摘要："Amyloidogenesis is one of the key pathophysiological changes in Alzheimer's disease (AD). Accumulation of the toxic A beta results from the catalytic processing of beta-amyloid precursor protein (APP) associated beta-amyloid converting enzyme 1 (BACE1) activity. It is reported that dead-box helicase 17 (DDX17) controls RNA metabolism and is involved in the development of multiple diseases. However, whether DDX17 might play a role in amyloidogenesis has not been documented. In the present study, we found that DDX17 protein level was significantly increased in HEK and SH-SY5Y cells that stably express full-length APP (HEK-APP and Y5Y-APP) and in the brain of APP/PS1 mice, an animal model of AD. DDX17 knockdown, as opposed to DDX17 overexpression, markedly reduced the protein levels of BACE1 and the beta-amyloid peptide (A beta) in Y5Y-APP cells. We further found that DDX17-mediated enhancement of BACE1 was selectively attenuated by translation inhibitors. Specifically, DDX17 selectively interacted with the 5 ' untranslated region (5 ' UTR) of BACE1 mRNA, and deletion of the 5 ' UTR abolished the effect of DDX17 on luciferase activity or protein level of BACE1. Here, we show that the enhanced expression of DDX17 in AD was associated with amyloidogenesis; through the 5 ' UTR-dependent BACE1 translation, DDX17 might serve as an important mediator contributing to the progression of AD."

基金机构："National Natural Science Foundation of China [81971030, 82271461]; Chongqing Education commission [KJZD-K201900404]"

基金资助正文：This research was funded by the National Natural Science Foundation of China (81971030 and 82271461) and Chongqing Education commission (KJZD-K201900404).