DC Field | Value | Language |
---|---|---|
dc.contributor.author | Soper, Molly T. | ko |
dc.contributor.author | DeToma, Alaina S. | ko |
dc.contributor.author | Hyung, Suk-Joon | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.contributor.author | Ruotolo, Brandon T. | ko |
dc.date.accessioned | 2018-02-21T06:24:51Z | - |
dc.date.available | 2018-02-21T06:24:51Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2013-06 | - |
dc.identifier.citation | PHYSICAL CHEMISTRY CHEMICAL PHYSICS, v.15, no.23, pp.8952 - 8961 | - |
dc.identifier.issn | 1463-9076 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240307 | - |
dc.description.abstract | Recently, small peptides have been shown to modulate aggregation and toxicity of the amyloid-beta protein (A beta). As such, these new scaffolds may help discover a new class of biotherapeutics useful in the treatment of Alzheimer's disease. Many of these inhibitory peptide sequences have been derived from natural sources or from Ab itself (e.g., C-terminal A beta fragments). In addition, much earlier work indicates that tachykinins, a broad class of neuropeptides, display neurotrophic properties, presumably through direct interactions with either A beta or its receptors. Based on this work, we undertook a limited screen of neuropeptides using ion mobility-mass spectrometry to search for similar such peptides with direct A beta binding properties. Our results reveal that the neuropeptides leucine enkephalin (LE) and galanin interact with both the monomeric and small oligomeric forms of A beta(1-40) to create a range of complexes having diverse stoichiometries, while some tachyknins (i.e., substance P) do not. LE interacts with A beta more strongly than galanin, and we utilized ion mobility-mass spectrometry, molecular dynamics simulations, gel electrophoresis/Western blot, and transmission electron microscopy to study the influence of this peptide on the structure of A beta monomer, small A beta oligomers, as well as the eventual formation of A beta fibrils. We find that LE binds selectively within a region of A beta between its N-terminal tail and hydrophobic core. Furthermore, our data indicate that LE modulates fibril generation, producing shorter fibrillar aggregates when added in stoichiometric excess relative to A beta. | - |
dc.language | English | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.title | Amyloid-beta-neuropeptide interactions assessed by ion mobility-mass spectrometry | - |
dc.type | Article | - |
dc.identifier.wosid | 000319285000010 | - |
dc.identifier.scopusid | 2-s2.0-84878055789 | - |
dc.type.rims | ART | - |
dc.citation.volume | 15 | - |
dc.citation.issue | 23 | - |
dc.citation.beginningpage | 8952 | - |
dc.citation.endingpage | 8961 | - |
dc.citation.publicationname | PHYSICAL CHEMISTRY CHEMICAL PHYSICS | - |
dc.identifier.doi | 10.1039/c3cp50721a | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Soper, Molly T. | - |
dc.contributor.nonIdAuthor | DeToma, Alaina S. | - |
dc.contributor.nonIdAuthor | Hyung, Suk-Joon | - |
dc.contributor.nonIdAuthor | Ruotolo, Brandon T. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | PROTEIN COMPLEXES | - |
dc.subject.keywordPlus | GAS-PHASE | - |
dc.subject.keywordPlus | AGGREGATION | - |
dc.subject.keywordPlus | PEPTIDES | - |
dc.subject.keywordPlus | OLIGOMERIZATION | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | NEUROTOXICITY | - |
dc.subject.keywordPlus | PROTEOMICS | - |
dc.subject.keywordPlus | DERIVATIVES | - |
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