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

biorxiv. 2019; 
Yan?Wang, ?Meiling?Lian, ?Jing?Zhou, ??View Shengzhou?Wu
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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 a... More

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