Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 손형진 | - |
dc.date.accessioned | 2017-12-28T16:32:04Z | - |
dc.date.available | 2017-12-28T16:32:04Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1553-7390 | - |
dc.identifier.other | OAK-21253 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/239600 | - |
dc.description.abstract | DJ-1 is one of the causative genes for early onset familiar Parkinson’s disease (PD) and is also considered to influence the pathogenesis of sporadic PD. DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species (ROS) levels. In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP+-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into α-ketoglutarate, was detected. Loss of IDH induced hyper-sensitivity to oxidative stress accompanying age-dependent mitochondrial defects and dopaminergic (DA) neuron degeneration in Drosophila, indicating its critical roles in maintaining mitochondrial integrity and DA neuron survival. Further genetic analysis suggested that DJ-1 controls IDH gene expression through nuclear factor-E2-related factor2 (Nrf2). Using Drosophila and mammalian DA models, we found that IDH suppresses intracellular and mitochondrial ROS level and subsequent DA neuron loss downstream of DJ-1. Consistently, trimethyl isocitrate (TIC), a cell permeable isocitrate, protected mammalian DJ-1 null DA cells from oxidative stress in an IDH-dependent manner. These results suggest that isocitrate and its derivatives are novel treatments for PD associated with DJ-1 dysfunction. © 2017 Yang et al. | - |
dc.language | English | - |
dc.publisher | Public Library of Science | - |
dc.title | Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH) | - |
dc.type | Article | - |
dc.relation.issue | 8 | - |
dc.relation.volume | 13 | - |
dc.relation.index | SCOPUS | - |
dc.relation.journaltitle | PLoS Genetics | - |
dc.identifier.doi | 10.1371/journal.pgen.1006975 | - |
dc.identifier.wosid | WOS:000408763800041 | - |
dc.identifier.scopusid | 2-s2.0-85028806689 | - |
dc.author.google | Yang J. | - |
dc.author.google | Kim M.J. | - |
dc.author.google | Yoon W. | - |
dc.author.google | Kim E.Y. | - |
dc.author.google | Kim H. | - |
dc.author.google | Lee Y. | - |
dc.author.google | Min B. | - |
dc.author.google | Kang K.S. | - |
dc.author.google | Son J.H. | - |
dc.author.google | Park H.T. | - |
dc.author.google | Chung J. | - |
dc.author.google | Koh H. | - |
dc.contributor.scopusid | 손형진(7203086503) | - |
dc.date.modifydate | 20220119162545 | - |