资源 » 参考数据库 » 客户发表文献

至今，GenScript的服务及产品已被Cell, Nature, Science, PNAS等1300多家生物医药类杂志引用近万次，处于行业领先水平。NIH、哈佛、耶鲁、斯坦福、普林斯顿、杜克大学等约400家全球著名机构使用GenScript的基因合成、多肽服务、抗体服务和蛋白服务等成功地发表科研成果，再次证明GenScript 有能力帮助业内科学家Make research easy.

Dicer1 is reduced in APPswe/PSEN1dE9 mice and is regulated by Nrf2

biorxiv. 2019;

Yan Wang, Meiling Lian, Jing Zhou, View Shengzhou Wu

Products/Services Used	Details	Operation
Peptide Synthesis	Activated caspase 3 (Beyotime Biotechnology, Haimen, China, cat# AC033), βIII-tubulin (Beyotime Biotechnology, cat# AT809), Histone 3 (Beyotime Biotechnology, cat# AF0009), Vimentin (Beyotime Biotechnology, cat# AF1975), GAPDH (Bioworld, Nanjing, China, cat# MB001), NeuN (Beyotime Biotechnology, cat# AF1072). The following secondary antibodies were also used in this study: goat anti-mouse horseradish peroxidase conjugated IgG (Boster Biological Technology, Co. Ltd, Wuhan, China), goat anti-Rabbit horseradish peroxidase conjugated IgG (Boster Biological Technology). The following reagents or cell lines were used in this study: a human Aβ42 peptide (GenScript, Nanjing, China, cat# RP10017), the Dicer1 siRNA duplex and the negative control (NC) siRNA duplex (Genepharma, Suzhou, China), MTS reagent (CellTiter 96 AQueous One Solution, Promega, Beijing, China, cat# 3580), pfu High fidelity enzyme (Qiagen, Beijing, China, cat# KP202), pJet1.2 vector (Thermo Fisher Scientific, Carlsbad, CA,USA, cat# K1231), pGL6-basic (Beyotime Biotechnology, Haimen, China, cat# D2105), pRL-TK Vector (Beyotime Biotechnology, Inc, cat# D2762), a human pCMV-Nrf2 (Sino Biological, Beijing, China, cat# HG17384-U), a mouse pCMV-Nrf2 (Sino Biological, Beijing, China, cat# MG56971-UT), or an empty pCMV3 vector (Sino Biological, Beijing, China, cat# D2602), mitochondrial extraction kit (Beyotime Biotechnology, cat# C3601), 2’,7’-Dichlorodihydrofluorescein diacetate (Thermo fisher, Shanghai, China, cat# 2938), JC-1 probe solution (Sigma, St Louis, MO, USA, cat# CS0760), Neuro-2a (N2A)(ATCC, Manassas, VA cat# CCL-131, RRID:CVCL_0470), SK-N-BE(2) (ATCC Cat# CRL-2271, RRID:CVCL_0528).	Get A Quote

摘要

The pathogenesis of Alzheimer’s disease (AD) involves the central roles of oxidative stress. Oxidative stress due to Dicer1 depletion may underline the neurodegeneration in the central nervous system and degeneration of retinal pigment epithelial cells in geographic atrophy form of age-related macular degeneration. We hypothesized that Dicer1 may play roles in AD pathogenesis. Indeed, Dicer1 was reduced in the hippocampus and cortex of APPswe/PSEN1dE9 mice, an AD model. Dicer1 knockdown induced oxidative stress, mitochondrial dysfunction, apoptosis in cultured neurons, and increased secretions of interleukin-1β/-18, indicators of inflammasome activation. Accordingly, Dicer1 was decreased by amyloid peptide and the effect was connected with down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Anti-oxidant response elements (AREs) were identified in the promoter of Dicer1 and Keap1-Nrf2-AREs signaling was demonstrated to regulate Dicer1 expression. Furthermore, overexpression of Dicer1 carried by adenovirus in the cultured neurons rescued neurite deficit induced by amyloid peptide. In consistent with the in vitro results, injection of Dicer1-overexperssion adenovirus in the hippocampus of the AD mice significantly improved spatial learning. Altogether, we unveiled an unexploited roles of Dicer1 in AD and a novel way of Dicer1 regulation. These findings suggest that Dicer1 may be a target in AD therapy. Significance Statement Dicer1 is a microRNA-processing enzyme, which is central to microRNA maturation. For the first time, we herein reported that Dicer1 was reduced in the hippocampus or the cortex of AD mice before overt amyloid plque deposition and overexpression of Dicer1 in the hippocampus significantly improved spatial learning in AD mice. We also demonstrated that Dicer1 was regulated by Keap1-Nrf2-ARE signaling which is unreported before. These findings advance understandings of AD pathogenesis and suggest that Dicer1 may be a molecular target in AD therapy.