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DC Field | Value | Language |
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dc.citation.number | 1 | - |
dc.citation.startPage | e1007125 | - |
dc.citation.title | PLOS GENETICS | - |
dc.citation.volume | 14 | - |
dc.contributor.author | Offenburger, Sarah-Lena | - |
dc.contributor.author | Ho, Xue Yan | - |
dc.contributor.author | Tachie-Menson, Theresa | - |
dc.contributor.author | Coakley, Sean | - |
dc.contributor.author | Hilliard, Massimo A. | - |
dc.contributor.author | Gartner, Anton | - |
dc.date.accessioned | 2023-12-21T21:12:34Z | - |
dc.date.available | 2023-12-21T21:12:34Z | - |
dc.date.created | 2019-09-10 | - |
dc.date.issued | 2018-01 | - |
dc.description.abstract | Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson's disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting Caenorhabditis elegans dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the transthyretin-related gene ttr-33. The only described C. elegans transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33 have distinct roles. TTR-33 is likely produced in the posterior arcade cells in the head of C. elegans larvae and is predicted to be a secreted protein. TTR-33 protects C. elegans from oxidative stress induced by paraquat or H2O2 at an organismal level. The increased oxidative stress sensitivity of ttr-33 mutants is alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic evidence that the C. elegans cell corpse engulfment pathway is required for the degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we describe a new neuroprotective mechanism and demonstrate that TTR-33 normally functions to protect dopaminergic neurons from oxidative stress-induced degeneration, potentially by acting as a secreted sensor or scavenger of oxidative stress. | - |
dc.identifier.bibliographicCitation | PLOS GENETICS, v.14, no.1, pp.e1007125 | - |
dc.identifier.doi | 10.1371/journal.pgen.1007125 | - |
dc.identifier.issn | 1553-7404 | - |
dc.identifier.scopusid | 2-s2.0-85041297867 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/27475 | - |
dc.identifier.url | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007125 | - |
dc.identifier.wosid | 000423718600004 | - |
dc.language | 영어 | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.title | 6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is promoted by the engulfment pathway and inhibited by the transthyretin-related protein TTR-33 | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | PHAGOCYTOSIS | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordPlus | PREDICTION | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | PROGRAMMED CELL-DEATH | - |
dc.subject.keywordPlus | LIFE-SPAN | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | C-ELEGANS | - |
dc.subject.keywordPlus | STRESS | - |
dc.subject.keywordPlus | DEGENERATION | - |
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