DC Field | Value | Language |
---|---|---|
dc.contributor.author | Korshavn, Kyle J. | ko |
dc.contributor.author | Satriano, Cristina | ko |
dc.contributor.author | Lin, Yuxi | ko |
dc.contributor.author | Zhang, Rongchun | ko |
dc.contributor.author | Dulchavsky, Mark | ko |
dc.contributor.author | Bhunia, Anirban | ko |
dc.contributor.author | Ivanova, Magdalena I. | ko |
dc.contributor.author | Lee, Young-Ho | ko |
dc.contributor.author | La Rosa, Carmelo | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.date.accessioned | 2018-02-21T06:05:49Z | - |
dc.date.available | 2018-02-21T06:05:49Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2017-03 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.292, no.11, pp.4638 - 4650 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240262 | - |
dc.description.abstract | The aggregation of amyloid-beta (A beta) on lipid bilayers has been implicated as Amechanism by which A beta exerts its toxicity in Alzheimer's disease (AD). Lipid bilayer thinning has been observed during both oxidative stress and protein aggregation in AD, but whether these pathological modifications of the bilayer correlate withA beta misfolding is unclear. Here, we studied peptide-lipid interactions in synthetic bilayers of the shortchain lipid dilauroyl phosphatidylcholine (DLPC) as Asimplified model for diseased bilayers to determine their impact on A beta aggregate, protofibril, and fibril formation. A beta aggregation and fibril formation in membranes composed of dioleoyl phosphatidylcholine (DOPC) or 1-palmitoyl-2-oleoyl phosphatidylcholine mimicking normal bilayers served as controls. Differences in aggregate formation and stability were monitored by a combination of thioflavin-T fluorescence, circular dichroism, atomic force microscopy, transmission electron microscopy, and NMR. Despite the ability of all three lipid bilayers to catalyze aggregation, DLPC accelerates aggregation at much lower concentrations and prevents the fibrillation of A beta at low micromolar concentrations. DLPC stabilized globular, membrane-associated oligomers, which could disrupt the bilayer integrity. DLPC bilayers also remodeled preformed amyloid fibrils into Apseudo-unfolded, molten globule state, which resembled on-pathway, protofibrillar aggregates. Whereas the stabilized, membrane-associated oligomers were found to be nontoxic, the remodeled species displayed toxicity similar to that of conventionally prepared aggregates. These results provide mechanistic insights into the roles that pathologically thin bilayers may play in A beta aggregation on neuronal bilayers, and pathological lipid oxidation may contribute to A beta misfolding. | - |
dc.language | English | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | SOLID-STATE NMR | - |
dc.subject | CRITICAL MICELLE CONCENTRATION | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | ALPHA-SYNUCLEIN | - |
dc.subject | A-BETA | - |
dc.subject | FIBRIL FORMATION | - |
dc.subject | MEMBRANE FRAGMENTATION | - |
dc.subject | PHOSPHOLIPID-BILAYERS | - |
dc.subject | HYDROPHOBIC MISMATCH | - |
dc.subject | PROTEIN AGGREGATION | - |
dc.title | Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid- beta | - |
dc.type | Article | - |
dc.identifier.wosid | 000397585100021 | - |
dc.identifier.scopusid | 2-s2.0-85015653668 | - |
dc.type.rims | ART | - |
dc.citation.volume | 292 | - |
dc.citation.issue | 11 | - |
dc.citation.beginningpage | 4638 | - |
dc.citation.endingpage | 4650 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.doi | 10.1074/jbc.M116.764092 | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Korshavn, Kyle J. | - |
dc.contributor.nonIdAuthor | Satriano, Cristina | - |
dc.contributor.nonIdAuthor | Lin, Yuxi | - |
dc.contributor.nonIdAuthor | Zhang, Rongchun | - |
dc.contributor.nonIdAuthor | Dulchavsky, Mark | - |
dc.contributor.nonIdAuthor | Bhunia, Anirban | - |
dc.contributor.nonIdAuthor | Ivanova, Magdalena I. | - |
dc.contributor.nonIdAuthor | Lee, Young-Ho | - |
dc.contributor.nonIdAuthor | La Rosa, Carmelo | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | SOLID-STATE NMR | - |
dc.subject.keywordPlus | CRITICAL MICELLE CONCENTRATION | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | ALPHA-SYNUCLEIN | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | FIBRIL FORMATION | - |
dc.subject.keywordPlus | MEMBRANE FRAGMENTATION | - |
dc.subject.keywordPlus | PHOSPHOLIPID-BILAYERS | - |
dc.subject.keywordPlus | HYDROPHOBIC MISMATCH | - |
dc.subject.keywordPlus | PROTEIN AGGREGATION | - |
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