Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Byun, J. | - |
dc.contributor.author | Son, Sm | - |
dc.contributor.author | Cha, M-Y | - |
dc.contributor.author | Shong, M. | - |
dc.contributor.author | Hwang, Y. J. | - |
dc.contributor.author | Kim, Y. | - |
dc.contributor.author | Ryu, H. | - |
dc.contributor.author | Moon, M. | - |
dc.contributor.author | Kim, K-S | - |
dc.contributor.author | Mook-Jung, I. | - |
dc.date.accessioned | 2024-01-20T07:01:47Z | - |
dc.date.available | 2024-01-20T07:01:47Z | - |
dc.date.created | 2021-09-05 | - |
dc.date.issued | 2015-06 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.uri | https://pubs.kist.re.kr/handle/201004/125392 | - |
dc.description.abstract | Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-beta (A beta), yet the pathways between A beta and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in A beta-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed A beta undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with A beta. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in A beta-treated cells. Conversely, Crif1 overexpression prevented A beta-induced mitochondrial dysfunction and cell death. Finally, we show that A beta-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying A beta-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD. | - |
dc.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | ATP SYNTHASE | - |
dc.subject | NEURODEGENERATIVE DISEASES | - |
dc.subject | CELL-PROLIFERATION | - |
dc.subject | CRISTAE MORPHOLOGY | - |
dc.subject | CORTICAL-NEURONS | - |
dc.subject | PLAQUE-FORMATION | - |
dc.subject | TRANSGENIC MICE | - |
dc.subject | ANIMAL-MODEL | - |
dc.subject | IN-VIVO | - |
dc.title | CR6-interacting factor 1 is a key regulator in A beta-induced mitochondrial disruption and pathogenesis of Alzheimer's disease | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/cdd.2014.184 | - |
dc.description.journalClass | 1 | - |
dc.identifier.bibliographicCitation | CELL DEATH AND DIFFERENTIATION, v.22, no.6, pp.959 - 973 | - |
dc.citation.title | CELL DEATH AND DIFFERENTIATION | - |
dc.citation.volume | 22 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 959 | - |
dc.citation.endPage | 973 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.identifier.wosid | 000353916700009 | - |
dc.identifier.scopusid | 2-s2.0-84939985504 | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | ATP SYNTHASE | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | CELL-PROLIFERATION | - |
dc.subject.keywordPlus | CRISTAE MORPHOLOGY | - |
dc.subject.keywordPlus | CORTICAL-NEURONS | - |
dc.subject.keywordPlus | PLAQUE-FORMATION | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | ANIMAL-MODEL | - |
dc.subject.keywordPlus | IN-VIVO | - |
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