DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gorman, PM | - |
dc.contributor.author | Kim, S | - |
dc.contributor.author | Guo, M | - |
dc.contributor.author | Melnyk, RA | - |
dc.contributor.author | McLaurin, J | - |
dc.contributor.author | Fraser, PE | - |
dc.contributor.author | Bowie, JU | - |
dc.contributor.author | Chakrabartty, A | - |
dc.date.accessioned | 2015-06-25T01:35:03Z | - |
dc.date.available | 2015-06-25T01:35:03Z | - |
dc.date.created | 2009-03-18 | - |
dc.date.issued | 2008-01-30 | - |
dc.identifier.issn | 1471-2202 | - |
dc.identifier.other | 2015-OAK-0000007586 | en_US |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/9859 | - |
dc.description.abstract | Background: Amyloid precursor protein (APP) is enzymatically cleaved by gamma secretase to form two peptide products, either A beta 40 or the more neurotoxic A beta 42. The A beta 42/40 ratio is increased in many cases of familial Alzheimer's disease ( FAD). The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains. Results: Using synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers. Conclusion: The dissociation constants are correlated to both the A beta 42/A beta 40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce A beta production and A beta 42/A beta 40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and gamma- secretase components, potentially revealing a new class of gamma-secretase inhibitors. | - |
dc.description.statementofresponsibility | open | en_US |
dc.language | English | - |
dc.publisher | BIOMED CENTRAL LTD | - |
dc.relation.isPartOf | BMC NEUROSCIENCE | - |
dc.rights | BY_NC_ND | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/2.0/kr | en_US |
dc.title | Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants | - |
dc.type | Article | - |
dc.contributor.college | 생명과학과 | en_US |
dc.identifier.doi | 10.1186/1471-2202-9-17 | - |
dc.author.google | Gorman, PM | en_US |
dc.author.google | Kim, S | en_US |
dc.author.google | Chakrabartty, A | en_US |
dc.author.google | Bowie, JU | en_US |
dc.author.google | Fraser, PE | en_US |
dc.author.google | McLaurin, J | en_US |
dc.author.google | Melnyk, RA | en_US |
dc.author.google | Guo, M | en_US |
dc.relation.volume | 9 | en_US |
dc.contributor.id | 10136479 | en_US |
dc.relation.journal | BMC NEUROSCIENCE | en_US |
dc.relation.index | SCI급, SCOPUS 등재논문 | en_US |
dc.relation.sci | SCIE | en_US |
dc.collections.name | Journal Papers | en_US |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | BMC NEUROSCIENCE, v.9 | - |
dc.identifier.wosid | 000253965800001 | - |
dc.date.tcdate | 2019-01-01 | - |
dc.citation.title | BMC NEUROSCIENCE | - |
dc.citation.volume | 9 | - |
dc.contributor.affiliatedAuthor | Kim, S | - |
dc.identifier.scopusid | 2-s2.0-40549088246 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 51 | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | MISSENSE MUTATION | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | PEPTIDES | - |
dc.subject.keywordPlus | DIMER | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | PROTEOLYSIS | - |
dc.subject.keywordPlus | PRESENILIN | - |
dc.subject.keywordPlus | CLEAVAGE | - |
dc.subject.keywordPlus | PROTEASE | - |
dc.subject.keywordPlus | ENZYME | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
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