DC Field | Value | Language |
---|---|---|
dc.contributor.author | Beck, Michael W. | ko |
dc.contributor.author | Oh, Shin Bi | ko |
dc.contributor.author | Kerr, Richard A. | ko |
dc.contributor.author | Lee, Hyuck Jin | ko |
dc.contributor.author | Kim, So Hee | ko |
dc.contributor.author | Kim, Sujeong | ko |
dc.contributor.author | Jang, Milim | ko |
dc.contributor.author | Ruotolo, Brandon T. | ko |
dc.contributor.author | Lee, Joo-Yong | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2018-02-21T06:06:29Z | - |
dc.date.available | 2018-02-21T06:06:29Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2015-03 | - |
dc.identifier.citation | CHEMICAL SCIENCE, v.6, no.3, pp.1879 - 1886 | - |
dc.identifier.issn | 2041-6520 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240285 | - |
dc.description.abstract | Multiple factors, including amyloid-beta (A beta), metals, and reactive oxygen species (ROS), are involved in the development of Alzheimer's disease (AD). Metal ions can interact with A beta species generating toxic oligomers and ROS in vitro; however, the involvement of metal-A beta complexes in AD pathology in vivo remains unclear. To solve this uncertainty, we have developed a chemical tool (L2-b) that specifically targets metal-A beta complexes and modulates their reactivity (i.e., metal-A beta aggregation, toxic oligomer formation, and ROS production). Through the studies presented herein, we demonstrate that L2-b is able to specifically interact with metal-A beta complexes over metal-free A beta analogues, redirect metal-A beta aggregation into off-pathway, nontoxic less structured A beta aggregates, and diminish metal-A beta-induced ROS production, overall mitigating metal-A beta-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-A beta 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-A beta complexes, we report for the first time experimental evidence that metal-A beta complexes are related directly to AD pathogenesis. | - |
dc.language | English | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.title | A rationally designed small molecule for identifying an in vivo link between metal-amyloid-beta complexes and the pathogenesis of Alzheimer's disease | - |
dc.type | Article | - |
dc.identifier.wosid | 000349832600032 | - |
dc.identifier.scopusid | 2-s2.0-84923167087 | - |
dc.type.rims | ART | - |
dc.citation.volume | 6 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 1879 | - |
dc.citation.endingpage | 1886 | - |
dc.citation.publicationname | CHEMICAL SCIENCE | - |
dc.identifier.doi | 10.1039/c4sc03239j | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Beck, Michael W. | - |
dc.contributor.nonIdAuthor | Oh, Shin Bi | - |
dc.contributor.nonIdAuthor | Kerr, Richard A. | - |
dc.contributor.nonIdAuthor | Lee, Hyuck Jin | - |
dc.contributor.nonIdAuthor | Kim, So Hee | - |
dc.contributor.nonIdAuthor | Kim, Sujeong | - |
dc.contributor.nonIdAuthor | Jang, Milim | - |
dc.contributor.nonIdAuthor | Ruotolo, Brandon T. | - |
dc.contributor.nonIdAuthor | Lee, Joo-Yong | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
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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