國家衛生研究院 NHRI:Item 3990099045/12296
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 853601      Online Users : 1059
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12296


    Title: NPGPx-mediated adaptation to oxidative stress protects motor neurons from degeneration in aging by directly modulating O-GlcNAcase
    Authors: Hsieh, YL;Su, FY;Tsai, LK;Huang, CC;Ko, YL;Su, LW;Chen, KY;Shih, HM;Hu, CM;Lee, WH
    Contributors: Institute of Molecular and Genomic Medicine
    Abstract: 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.
    Date: 2019-11
    Relation: 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
    Appears in Collections:[Hsiu-Ming Shih] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    SCP85074993516.pdf5326KbAdobe PDF387View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

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