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000006518 0247_ $$2DOI$$a10.1021/bi900818a
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000006518 084__ $$2WoS$$aBiochemistry & Molecular Biology
000006518 1001_ $$0P:(DE-HGF)0$$aSchlenzig, D.$$b0
000006518 245__ $$aPyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. A driving force in different neurodegenerative disorders?
000006518 260__ $$aColumbus, Ohio$$bAmerican Chemical Society$$c2009
000006518 300__ $$a7072 - 7078
000006518 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000006518 440_0 $$0798$$aBiochemistry$$v48$$x0006-2960$$y29
000006518 500__ $$aRecord converted from VDB: 12.11.2012
000006518 520__ $$aN-Terminally truncated and pyroglutamate (pGlu) modified amyloid beta (Abeta) peptides are major constituents of amyloid deposits in sporadic and inherited Alzheimer's disease (AD). Formation of pGlu at the N-terminus confers resistance against cleavage by most aminopeptidases, increases toxicity of the peptides, and may seed Abeta aggregate formation. Similarly, the deposited amyloid peptides ABri and ADan, which cause a very similar histopathology in familial British dementia (FBD) and familial Danish dementia (FDD), are N-terminally blocked by pGlu. Triggered by the coincidence of pGlu-modified amyloid peptides and similar pathology in AD, FBD, and FDD, we investigated the impact of N-terminal pGlu on biochemical and biophysical properties of Abeta, ABri, and ADan. N-Terminal pGlu increases the hydrophobicity and changes the pH-dependent solubility profile, rendering the pGlu-modified peptides less soluble in the basic pH range. The pGlu residue increases the aggregation propensity of all amyloid peptides as evidenced by ThT fluorescence assays and dynamic light scattering. The far-UV CD spectroscopic analysis points toward an enhanced beta-sheet structure of the pGlu-Abeta. Importantly, changes in fibril morphology are clearly caused by the N-terminal pGlu, resulting in the formation of short fibers, which are frequently arranged in bundles. The effect of pGlu on the morphology is virtually indistinguishable between ABri, ADan, and Abeta. The data provide evidence for a comparable influence of the pGlu modification on the aggregation process of structurally different amyloid peptides, thus likely contributing to the molecularly distinct neurodegenerative diseases AD, FBD, and FDD. The main driving force for the aggregation is apparently an increase in the hydrophobicity and thus an accelerated seed formation.
000006518 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
000006518 588__ $$aDataset connected to Web of Science, Pubmed
000006518 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000006518 650_2 $$2MeSH$$aAmino Acid Sequence
000006518 650_2 $$2MeSH$$aAmyloid: chemistry
000006518 650_2 $$2MeSH$$aAmyloid: metabolism
000006518 650_2 $$2MeSH$$aAmyloid: ultrastructure
000006518 650_2 $$2MeSH$$aCircular Dichroism
000006518 650_2 $$2MeSH$$aHumans
000006518 650_2 $$2MeSH$$aHydrogen-Ion Concentration
000006518 650_2 $$2MeSH$$aMicroscopy, Electron
000006518 650_2 $$2MeSH$$aMolecular Sequence Data
000006518 650_2 $$2MeSH$$aPeptides: chemistry
000006518 650_2 $$2MeSH$$aPeptides: metabolism
000006518 650_2 $$2MeSH$$aPyrrolidonecarboxylic Acid: metabolism
000006518 650_2 $$2MeSH$$aSolubility
000006518 650_2 $$2MeSH$$aSpectrophotometry, Ultraviolet
000006518 650_7 $$00$$2NLM Chemicals$$aAmyloid
000006518 650_7 $$00$$2NLM Chemicals$$aPeptides
000006518 650_7 $$098-79-3$$2NLM Chemicals$$aPyrrolidonecarboxylic Acid
000006518 650_7 $$2WoSType$$aJ
000006518 7001_ $$0P:(DE-HGF)0$$aManhart, S.$$b1
000006518 7001_ $$0P:(DE-Juel1)VDB88687$$aCinar, Y.$$b2$$uFZJ
000006518 7001_ $$0P:(DE-Juel1)132029$$aWillbold, D.$$b3$$uFZJ
000006518 7001_ $$0P:(DE-Juel1)VDB65869$$aFunke, S. A.$$b4$$uFZJ
000006518 7001_ $$0P:(DE-HGF)0$$aKleinschmidt, M.$$b5
000006518 7001_ $$0P:(DE-HGF)0$$aHause, G.$$b6
000006518 7001_ $$0P:(DE-HGF)0$$aSchilling, S.$$b7
000006518 7001_ $$0P:(DE-HGF)0$$aDemuth, H.-U.$$b8
000006518 773__ $$0PERI:(DE-600)1472258-6$$a10.1021/bi900818a$$gVol. 48, p. 7072 - 7078$$p7072 - 7078$$q48<7072 - 7078$$tBiochemistry$$v48$$x0006-2960$$y2009
000006518 8567_ $$uhttp://dx.doi.org/10.1021/bi900818a
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000006518 9141_ $$y2009
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