國家衛生研究院 NHRI:Item 3990099045/12296
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 908285      在线人数 : 963
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧:
  • 您可在西文检索词汇前后加上"双引号",以获取较精准的检索结果
  • 若欲以作者姓名搜寻,建议至进阶搜寻限定作者字段,可获得较完整数据
  • 进阶搜寻
    主页登入上传说明关于NHRI管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/12296


    题名: NPGPx-mediated adaptation to oxidative stress protects motor neurons from degeneration in aging by directly modulating O-GlcNAcase
    作者: Hsieh, YL;Su, FY;Tsai, LK;Huang, CC;Ko, YL;Su, LW;Chen, KY;Shih, HM;Hu, CM;Lee, WH
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, usually occurs in middle-aged people. However, the molecular basis of age-related cumulative stress in ALS pathogenesis remains elusive. Here, we found that mice deficient in NPGPx (GPx7), an oxidative stress sensor, develop ALS-like phenotypes, including paralysis, muscle denervation, and motor neurons loss. Unlike normal spinal motor neurons that exhibit elevated O-GlcNAcylation against age-dependent oxidative stress, NPGPx-deficient spinal motor neurons fail to boost O-GlcNAcylation and exacerbate ROS accumulation, leading to cell death. Mechanistically, stress-activated NPGPx inhibits O-GlcNAcase (OGA) through disulfide bonding to fine-tune global O-GlcNAcylation. Pharmacological inhibition of OGA rescues spinal motor neuron loss in aged NPGPx-deficient mice. Furthermore, expression of NPGPx in ALS patients is significantly lower than in unaffected adults. These results suggest that NPGPx modulates O-GlcNAcylation by inhibiting OGA to cope with age-dependent oxidative stress and protect motor neurons from degeneration, providing a potential therapeutic axis for ALS. Hsieh et al. uncover an adaptive mechanism mediated by NPGPx in modulating O-GlcNAcylation to cope with chronic oxidative stress in aging. Stress-activated NPGPx restrains OGA activity through disulfide bonding and elevates O-GlcNAcylation to protect motor neurons from degeneration.
    日期: 2019-11
    關聯: Cell Reports. 2019 Nov;29(8):2134-2143.
    Link to: http://dx.doi.org/10.1016/j.celrep.2019.10.053
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2211-1247&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000497954200003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85074993516
    显示于类别:[施修明] 期刊論文

    文件中的档案:

    档案 描述 大小格式浏览次数
    SCP85074993516.pdf5326KbAdobe PDF387检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈