https://scholars.lib.ntu.edu.tw/handle/123456789/587967
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Hsieh Y.-L. | en_US |
dc.contributor.author | Su F.-Y. | en_US |
dc.contributor.author | LI-KAI TSAI | en_US |
dc.contributor.author | Huang C.-C. | en_US |
dc.contributor.author | Ko Y.-L. | en_US |
dc.contributor.author | Su L.-W. | en_US |
dc.contributor.author | Chen K.-Y. | en_US |
dc.contributor.author | Shih H.-M. | en_US |
dc.contributor.author | Hu C.-M. | en_US |
dc.contributor.author | Lee W.-H. | en_US |
dc.date.accessioned | 2021-11-26T05:56:27Z | - |
dc.date.available | 2021-11-26T05:56:27Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 22111247 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074993516&doi=10.1016%2fj.celrep.2019.10.053&partnerID=40&md5=9a918ad466a0ac7de21d93f22b156a4e | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/587967 | - |
dc.description.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. ? 2019 The Author(s) | - |
dc.relation.ispartof | Cell Reports | - |
dc.subject | aging; ALS; motor neuron; NPGPx; O-GlcNAcylation; OGA; oxidative stress | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | hydrolase; NPGPx protein; o GlcNAcase; phospholipid hydroperoxide glutathione peroxidase; reactive oxygen metabolite; unclassified drug; beta n acetylhexosaminidase; hexosaminidase C; acylation; adaptation; adult; aged; aging; amyotrophic lateral sclerosis; animal cell; animal experiment; animal model; Article; cell death; clinical article; controlled study; disulfide bond; enzyme inhibition; female; gene; gene expression; human; human cell; male; motoneuron; mouse; nerve cell degeneration; nonhuman; NPGPx gene; oxidative stress; priority journal; aging; amyotrophic lateral sclerosis; animal; genetics; metabolism; motoneuron; muscle denervation; mutant mouse strain; oxidative stress; paralysis; physiology; Aging; Amyotrophic Lateral Sclerosis; Animals; beta-N-Acetylhexosaminidases; Female; Humans; Mice; Mice, Mutant Strains; Motor Neurons; Muscle Denervation; Oxidative Stress; Paralysis | - |
dc.title | NPGPx-Mediated Adaptation to Oxidative Stress Protects Motor Neurons from Degeneration in Aging by Directly Modulating O-GlcNAcase | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1016/j.celrep.2019.10.053 | - |
dc.identifier.pmid | 31747588 | - |
dc.identifier.scopus | 2-s2.0-85074993516 | - |
dc.relation.pages | 2134-2143.e7 | - |
dc.relation.journalvolume | 29 | - |
dc.relation.journalissue | 8 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Neurology-NTUH | - |
crisitem.author.dept | Neurology | - |
crisitem.author.dept | The Clinical Center for Neuroscience and Behavior | - |
crisitem.author.orcid | 0000-0001-8420-6951 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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