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DE-627 |
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20231224154621.0 |
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231224s2015 xx |||||o 00| ||eng c |
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|a 10.1021/acs.langmuir.5b01108
|2 doi
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|a pubmed24n0833.xml
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|a (DE-627)NLM249918277
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|a (NLM)26070334
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Xie, Baolong
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Multifunctionality of Acidulated Serum Albumin on Inhibiting Zn²⁺-Mediated Amyloid β-Protein Fibrillogenesis and Cytotoxicity
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|c 2015
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 05.04.2016
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|a Date Revised 09.03.2022
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Fibrillogenesis of amyloid β-proteins (Aβ) mediated by transition-metal ions such as Zn(2+) in neuronal cells plays a causative role in Alzheimer's disease. Hence, it is highly desired to design multifunctional agents capable of inhibiting Aβ aggregation and modulating metal-Aβ species. In this study, we fabricated acidulated human serum albumin (A-HSA) as a multifunctional agent for binding Zn(2+) and modulating Zn(2+)-mediated Aβ fibrillogenesis and cytotoxicity. On average, 19.5 diglycolic anhydrides were modified onto the surface of human serum albumin (HSA). It was confirmed that A-HSA kept the stability and biocompatibility of native HSA. Moreover, it could inhibit Aβ42 fibrillogenesis and change the pathway of Zn(2+)-mediated Aβ42 aggregation, as demonstrated by extensive biophysical assays. In addition, upon incubation with A-HSA, the cytotoxicity presented by Zn(2+)-Aβ42 aggregates was significantly mitigated in living cells. The results showed that A-HSA had much stronger inhibitory effect on Zn(2+)-mediated Aβ42 fibrillogenesis and cytotoxicity than equimolar HSA. Isothermal titration calorimetry and stopped-flow fluorescence measurements were then performed to investigate the working mechanism of A-HSA. The studies showed that the A-HSA surface, with more negative charges, not only had stronger affinity for Zn(2+) but also might decrease the binding affinity of Aβ42 for Zn(2+). Moreover, hydrophobic binding and electrostatic repulsion could work simultaneously on the bound Aβ42 on the A-HSA surface. As a result, Aβ42 conformations could be stretched, which avoided the formation of toxic Zn(2+)-Aβ42 aggregates. The research thus revealed that A-HSA is a multifunctional agent capable of altering the pathway of Zn(2+)-mediated Aβ42 aggregation and greatly mitigating the amyloid cytotoxicity
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Amyloid beta-Peptides
|2 NLM
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| 650 |
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7 |
|a Peptide Fragments
|2 NLM
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| 650 |
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|a Serum Albumin
|2 NLM
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| 650 |
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|a amyloid beta-protein (1-42)
|2 NLM
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| 650 |
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|a Zinc
|2 NLM
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| 650 |
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|a J41CSQ7QDS
|2 NLM
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| 700 |
1 |
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|a Dong, Xiaoyan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wang, Yongjian
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Sun, Yan
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Langmuir : the ACS journal of surfaces and colloids
|d 1992
|g 31(2015), 26 vom: 07. Juli, Seite 7374-80
|w (DE-627)NLM098181009
|x 1520-5827
|7 nnns
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| 773 |
1 |
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|g volume:31
|g year:2015
|g number:26
|g day:07
|g month:07
|g pages:7374-80
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| 856 |
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|u http://dx.doi.org/10.1021/acs.langmuir.5b01108
|3 Volltext
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|h 7374-80
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