Full metadata record
DC Field | Value | Language |
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dc.citation.endPage | 1886 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1879 | - |
dc.citation.title | CHEMICAL SCIENCE | - |
dc.citation.volume | 6 | - |
dc.contributor.author | Beck, Michael W. | - |
dc.contributor.author | Oh, Shin Bi | - |
dc.contributor.author | Kerr, Richard A. | - |
dc.contributor.author | Lee, Hyuck Jin | - |
dc.contributor.author | Kim, So Hee | - |
dc.contributor.author | Kim, Sujeong | - |
dc.contributor.author | Jang, Milim | - |
dc.contributor.author | Ruotolo, Brandon T. | - |
dc.contributor.author | Lee, Joo-Yong | - |
dc.contributor.author | Lim, Mi Hee | - |
dc.date.accessioned | 2023-12-22T01:38:02Z | - |
dc.date.available | 2023-12-22T01:38:02Z | - |
dc.date.created | 2015-03-19 | - |
dc.date.issued | 2015-03 | - |
dc.description.abstract | Multiple factors, including amyloid-β (Aβ), metals, and reactive oxygen species (ROS), are involved in the development of Alzheimer's disease (AD). Metal ions can interact with Aβ species generating toxic oligomers and ROS in vitro; however, the involvement of metal-Aβ complexes in AD pathology in vivo remains unclear. To solve this uncertainty, we have developed a chemical tool (L2-b) that specifically targets metal-Aβ complexes and modulates their reactivity (i.e., metal-Aβ aggregation, toxic oligomer formation, and ROS production). Through the studies presented herein, we demonstrate that L2-b is able to specifically interact with metal-Aβ complexes over metal-free Aβ analogues, redirect metal-Aβ aggregation into off-pathway, nontoxic less structured Aβ aggregates, and diminish metal-Aβ-induced ROS production, overall mitigating metal-Aβ-triggered toxicity, confirmed by multidisciplinary approaches. L2-b is also verified to enter the brain in vivo with relative metabolic stability. Most importantly, upon treatment of 5XFAD AD mice with L2-b, (i) metal-Aβ complexes are targeted and modulated in the brain; (ii) amyloid pathology is reduced; and (iii) cognition deficits are significantly improved. To the best of our knowledge, by employing an in vivo chemical tool specifically prepared for investigating metal-Aβ complexes, we report for the first time experimental evidence that metal-Aβ complexes are related directly to AD pathogenesis. | - |
dc.identifier.bibliographicCitation | CHEMICAL SCIENCE, v.6, no.3, pp.1879 - 1886 | - |
dc.identifier.doi | 10.1039/c4sc03239j | - |
dc.identifier.issn | 2041-6520 | - |
dc.identifier.scopusid | 2-s2.0-84923167087 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/10923 | - |
dc.identifier.url | http://pubs.rsc.org/en/Content/ArticleLanding/2015/SC/C4SC03239J#!divAbstract | - |
dc.identifier.wosid | 000349832600032 | - |
dc.language | 영어 | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.title | A rationally designed small molecule for identifying an in vivo link between metal-amyloid-β complexes and the pathogenesis of Alzheimer's disease | - |
dc.type | Article | - |
dc.description.isOpenAccess | TRUE | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | ZINC | - |
dc.subject.keywordPlus | COPPER | - |
dc.subject.keywordPlus | AGGREGATION | - |
dc.subject.keywordPlus | CLIOQUINOL | - |
dc.subject.keywordPlus | CHEMISTRY | - |
dc.subject.keywordPlus | OLIGOMERS | - |
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