DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Jung-Suk | ko |
dc.contributor.author | Braymer, Joseph J. | ko |
dc.contributor.author | Nanga, Ravi P. R. | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.date.accessioned | 2018-02-21T06:25:14Z | - |
dc.date.available | 2018-02-21T06:25:14Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2010-12 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.51, pp.21990 - 21995 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240322 | - |
dc.description.abstract | The accumulation of metal ions and amyloid-beta (A beta) aggregates found in the brain of patients with Alzheimer's disease (AD) has been suggested to be involved in AD pathogenesis. To investigate metal-A beta-associated pathways in AD, development of chemical tools to target metal-A beta species is desired. Only a few efforts, however, have been reported. Here, we report bifunctional small molecules, N-(pyridin-2-ylmethyl) aniline (L2-a) and N(1), N(1)-dimethyl-N(4)-(pyridin-2-ylmethyl)benzene-1,4-diamine (L2-b) that can interact with both metal ions and A beta species, as determined by spectroscopic methods including high-resolution NMR spectroscopy. Using the bifunctional compound L2-b, metal-induced A beta aggregation and neurotoxicity were modulated in vitro as well as in human neuroblastoma cells. Furthermore, treatment of human AD brain tissue homogenates containing metal ions and A beta species with L2-b showed disassembly of A beta aggregates. Therefore, our studies presented herein demonstrate the value of bifunctional compounds as chemical tools for investigating metal-A beta-associated events and their mechanisms in the development and pathogenesis of AD and as potential therapeutics. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.title | Design of small molecules that target metal-A beta species and regulate metal-induced A beta aggregation and neurotoxicity | - |
dc.type | Article | - |
dc.identifier.wosid | 000285521800014 | - |
dc.identifier.scopusid | 2-s2.0-78650669293 | - |
dc.type.rims | ART | - |
dc.citation.volume | 107 | - |
dc.citation.issue | 51 | - |
dc.citation.beginningpage | 21990 | - |
dc.citation.endingpage | 21995 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1006091107 | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Choi, Jung-Suk | - |
dc.contributor.nonIdAuthor | Braymer, Joseph J. | - |
dc.contributor.nonIdAuthor | Nanga, Ravi P. R. | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | amyloid-beta peptide | - |
dc.subject.keywordAuthor | copper | - |
dc.subject.keywordAuthor | zinc | - |
dc.subject.keywordAuthor | reactive oxygen species | - |
dc.subject.keywordAuthor | rational structure-based design | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | PROTEIN FIBRILLOGENESIS | - |
dc.subject.keywordPlus | AMYLOID PLAQUES | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | ZINC-BINDING | - |
dc.subject.keywordPlus | PEPTIDE | - |
dc.subject.keywordPlus | COPPER | - |
dc.subject.keywordPlus | NMR | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | PERMEABILITY | - |
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