共查询到20条相似文献,搜索用时 12 毫秒
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A Method for Evaluating the Level of Soluble β‐Amyloid(1–40/1–42) in Alzheimer’s Disease Based on the Binding of Gelsolin to β‐Amyloid Peptides 下载免费PDF全文
Dr. Yanyan Yu Lin Zhang Dr. Chenglin Li Xiaoyu Sun Dr. Daoquan Tang Prof. Guoyue Shi 《Angewandte Chemie (International ed. in English)》2014,53(47):12832-12835
In the present work, a new electrochemical strategy for the sensitive and specific detection of soluble β‐amyloid Aβ(1–40/1–42) peptides in a rat model of Alzheimer’s disease (AD) is described. In contrast to previous antibody‐based methods, β‐amyloid(1–40/1–42) was quantified based on its binding to gelsolin, a secretory protein present in the cerebrospinal fluid (CSF) and plasma. The level of soluble β‐amyloid peptides in the CSF and various brain regions were found with this method to be lower in rats with AD than in normal rats. 相似文献
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Valeria Castelletto Dr. Ian W. Hamley Prof. Rohan A. Hule Dr. Darrin Pochan Prof. 《Angewandte Chemie (International ed. in English)》2009,48(13):2317-2320
An addition to the family : The introduction of β‐amino acid residues into a modified amyloid β peptide fragment resulted in well‐defined helical nanoribbons (see cryo‐TEM image) comprising β strands mainly oriented perpendicular to the ribbon axis. The nanoribbons order into a flow‐aligning nematic phase at higher concentration. The β‐strand nanoribbon structure is an addition to the known set of secondary structures adopted by β‐peptides.
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Dr. Christofer Lendel Dr. Morten Bjerring Dr. Anatoly Dubnovitsky Robert T. Kelly Dr. Andrei Filippov Prof. Dr. Oleg N. Antzutkin Prof. Dr. Niels Chr. Nielsen Prof. Dr. Torleif Härd 《Angewandte Chemie (International ed. in English)》2014,53(47):12756-12760
Oligomeric and protofibrillar aggregates formed by the amyloid‐β peptide (Aβ) are believed to be involved in the pathology of Alzheimer’s disease. Central to Alzheimer pathology is also the fact that the longer Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40. Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid‐state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel‐like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C‐terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ42 forms oligomers and protofibrils more easily than Aβ40. 相似文献
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Yuko Murakoshi Dr. Tsuyoshi Takahashi Prof. Dr. Hisakazu Mihara 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(14):4525-4531
Aggregation of amyloid β‐peptide (Aβ) is closely related to the pathogenesis of Alzheimer’s disease (AD). Although much effort has been devoted to the construction of molecules that inhibit the aggregation of Aβ1‐42, high doses are needed for the inhibition of Aβ aggregation in many cases. Previously, we reported that designed green fluorescent protein (GFP) analogues that gives pseudo‐Aβ β‐sheet structures can work as an aggregation inhibitor against Aβ. To further test this design strategy, we constructed protein analogues that mimic Aβ β‐sheet structures of amyloids by using insulin‐like growth factor 2 receptor domain 11 (IGF2R‐d11) as a scaffold. A designed protein, named IG11KK, which has a parallel configuration of Aβ‐like β sheets, can bind more preferentially to oligomeric Aβ1‐42 than the monomer. Moreover, IG11KK suppressed the aggregation of Aβ1‐42 efficiently, even though lower concentrations of IG11KK than Aβ were used. The aggregation kinetics of Aβ in the presence of the designed proteins revealed that IG11KK can work as an inhibitor not only for the early to middle stages, but also in the latter stage of Aβ aggregation owing to its favorable binding to oligomeric structures of Aβ. The design strategy using β‐barrel proteins such as IGF2R‐d11 and GFP is useful in generating excellent inhibitors of protein misfolding and amyloid formation. 相似文献
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Attenuation of the Aggregation and Neurotoxicity of Amyloid‐β Peptides by Catalytic Photooxygenation 下载免费PDF全文
Dr. Atsuhiko Taniguchi Dr. Daisuke Sasaki Azusa Shiohara Prof. Takeshi Iwatsubo Dr. Taisuke Tomita Dr. Youhei Sohma Prof. Motomu Kanai 《Angewandte Chemie (International ed. in English)》2014,53(5):1382-1385
Alzheimer’s disease (AD), a progressive severe neurodegenerative disorder, is currently incurable, despite intensive efforts worldwide. Herein, we demonstrate that catalytic oxygenation of amyloid‐β peptides (Aβ) might be an effective approach to treat AD. Aβ1–42 was oxygenated under physiologically‐relevant conditions (pH 7.4, 37 °C) using a riboflavin catalyst and visible light irradiation, with modifications at the Tyr10, His13, His14, and Met35 residues. The oxygenated Aβ1–42 exhibited considerably lower aggregation potency and neurotoxicity compared with native Aβ. Photooxygenation of Aβ can be performed even in the presence of cells, by using a selective flavin catalyst attached to an Aβ‐binding peptide; the Aβ cytotoxicity was attenuated in this case as well. Furthermore, oxygenated Aβ1–42 inhibited the aggregation and cytotoxicity of native Aβ. 相似文献
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Dr. Vijaya B. Kenche Dr. Lin W. Hung Keyla Perez Irene Volitakes Dr. Guiseppe Ciccotosto Jeffrey Kwok Nicole Critch Nikki Sherratt Mikhalina Cortes Varsha Lal Prof. Colin L. Masters Kazuma Murakami Prof. Roberto Cappai Dr. Paul A. Adlard Prof. Kevin J. Barnham 《Angewandte Chemie (International ed. in English)》2013,52(12):3374-3378
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The Molecular Structure of Alzheimer β‐Amyloid Fibrils Formed in the Presence of Phospholipid Vesicles 下载免费PDF全文
Zheng Niu Weijing Zhao Dr. Zhengfeng Zhang Dr. Fanshu Xiao Xinqi Tang Prof. Jun Yang 《Angewandte Chemie (International ed. in English)》2014,53(35):9294-9297
β‐amyloid (Aβ) fibrils are the major species involved in Alzheimer’s disease (AD). An atomic‐resolution molecular structure of Aβ40 fibrils formed in the presence of lipid vesicles was obtained by using magic angle spinning (MAS) solid‐state NMR spectroscopy. The fibril structures formed in the presence of the lipid vesicles are remarkably different from those formed in solution. These results provide insights into the molecular mechanism of Aβ aggregation in the presence of lipid vesicles. 相似文献
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Multi‐Frequency,Multi‐Technique Pulsed EPR Investigation of the Copper Binding Site of Murine Amyloid β Peptide 下载免费PDF全文
Donghun Kim Dr. Jeong Kyu Bang Dr. Sun Hee Kim 《Angewandte Chemie (International ed. in English)》2015,54(5):1561-1564
Copper‐amyloid peptides are proposed to be the cause of Alzheimer’s disease, presumably by oxidative stress. However, mice do not produce amyloid plaques and thus do not suffer from Alzheimer’s disease. Although much effort has been focused on the structural characterization of the copper‐ human amyloid peptides, little is known regarding the copper‐binding mode in murine amyloid peptides. Thus, we investigated the structure of copper‐murine amyloid peptides through multi‐frequency, multi‐technique pulsed EPR spectroscopy in conjunction with specific isotope labeling. Based on our pulsed EPR results, we found that Ala2, Glu3, His6, and His14 are directly coordinated with the copper ion in murine amyloid β peptides at pH 8.5. This is the first detailed structural characterization of the copper‐binding mode in murine amyloid β peptides. This work may advance the knowledge required for developing inhibitors of Alzheimer’s disease. 相似文献
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Maintenance of Amyloid β Peptide Homeostasis by Artificial Chaperones Based on Mixed‐Shell Polymeric Micelles 下载免费PDF全文
Fan Huang Jianzu Wang Aoting Qu Liangliang Shen Dr. Jinjian Liu Jianfeng Liu Dr. Zhenkun Zhang Yingli An Prof. Linqi Shi 《Angewandte Chemie (International ed. in English)》2014,53(34):8985-8990
The disruption of Aβ homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer’s disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis in vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed‐shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM‐based chaperones can maintain Aβ homeostasis by a combination of inhibiting Aβ fibrillation and facilitating Aβ aggregate clearance and simultaneously reducing Aβ‐mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect. 相似文献
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Ana M. Saraiva Isabel Cardoso Maria João Saraiva Klaus Tauer M. Carmo Pereira Manuel A. N. Coelho Helmuth Möhwald Gerald Brezesinski 《Macromolecular bioscience》2010,10(10):1152-1163
The amyloid‐β peptide (Aβ) plays a central role in the mechanism of Alzheimer's disease, being the main constituent of the plaque deposits found in AD brains. Aβ amyloid formation and deposition are due to a conformational switching to a β‐enriched secondary structure. Our strategy to inhibit Aβ aggregation involves the re‐conversion of Aβ conformation by adsorption to nanoparticles. NPs were synthesized by sulfonation and sulfation of polystyrene, leading to microgels and latexes. Both polymeric nanostructures affect the conformation of Aβ inducing an unordered state. Oligomerization was delayed and cytotoxicity reduced. The proper balance between hydrophilic moieties and hydrophobic chains seems to be an essential feature of effective NPs.
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AD (Alzheimer’s disease) is a progressive neurodegenerative disorder characterized by the cerebral accumulation of fibrillar amyloid‐beta (Aβ) aggregates. Here we present the electrochemistry of two novel sym‐triazine derivatives (TAE‐1, TAE‐2) as modulators of Aβ1–42 aggregation in vitro. Incubation studies conducted at physiological conditions demonstrated strong inhibition of β‐sheet fibril formation. Uniquely, square‐wave voltammetry indicated progressive changes in the surface‐availability of amyloid‐intercalated triazines for oxidation, mediated by competing peptide self‐assembly. Time‐resolved voltammetric analysis showed increasing anodic peak currents (≥3‐fold) and progressive shifts in redox potentials, measured over 24 h. The more potent aggregation modulator (TAE‐2) showed prolonged association during the pre‐nucleation states of Aβ. 相似文献
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Sara Santi Dr. Valeria Musi Dr. Emiliano Descrovi Dr. Vincent Paeder Joab Di Francesco Dr. Lubos Hvozdara Dr. Peter van der Wal Prof. Hilal A. Lashuel Prof. Annalisa Pastore Prof. Reinhard Neier Prof. Hans Peter Herzig 《Chemphyschem》2013,14(15):3476-3482
We propose the application of a new label‐free optical technique based on photonic nanostructures to real‐time monitor the amyloid‐beta 1‐42 (Aβ(1‐42)) fibrillization, including the early stages of the aggregation process, which are related to the onset of the Alzheimer’s Disease (AD). The aggregation of Aβ peptides into amyloid fibrils has commonly been associated with neuronal death, which culminates in the clinical features of the incurable degenerative AD. Recent studies revealed that cell toxicity is determined by the formation of soluble oligomeric forms of Aβ peptides in the early stages of aggregation. At this phase, classical amyloid detection techniques lack in sensitivity. Upon a chemical passivation of the sensing surface by means of polyethylene glycol, the proposed approach allows an accurate, real‐time monitoring of the refractive index variation of the solution, wherein Aβ(1‐42) peptides are aggregating. This measurement is directly related to the aggregation state of the peptide throughout oligomerization and subsequent fibrillization. Our findings open new perspectives in the understanding of the dynamics of amyloid formation, and validate this approach as a new and powerful method to screen aggregation at early stages. 相似文献