ACS Chemical Neuroscience
·
2022
·
IF 5.78
Sijia Hao,Yayu Yang,Ailing Han,Jianan Chen,Xiaoyu Luo,Guozhen Fang,Jifeng Liu,Shuo Wang
Polyphenols are the class of naturally synthesized compounds in the secondary metabolism of plants, which are widely distributed in fruits and vegetables. Their potential health treatment strategies have attracted wide attention in the scientific community. The abnormal aggregation of Aβ to form mature fibrils is pathologically related to Alzheimer’s disease (AD). Therefore, inhibiting Aβ40 fibrillogenesis was considered to be the major method for the intervention and therapy of AD. Glycosides, as a cluster of natural phenolic compounds, are widely distributed in Chinese herbs, fruits, and vegetables. The inhibitory effect of glycosides (phloridzin, salidroside, polydatin, geniposide, and gastrodin) and their corresponding small molecules (phloretin, 4-hydroxyphenyl ethanol, resveratrol, genipin, and 4-hydroxybenzyl alcohol) on Aβ40 aggregation and fibrils prolongation, disaggregation against mature fibrils, and the resulting cytotoxicity were studied by systematical biochemical, cell biology and molecular docking techniques, respectively. As a result, all inhibitors were observed against Aβ40 aggregation and fibrils prolongation and disaggregated mature Aβ40 fibrils in a dose-dependent manner. Besides, the cell validity experiments also showed that all inhibitors could effectively alleviate the cytotoxicity induced by Aβ40 aggregates, and the glycoside groups played important roles in this inhibiting process. Finally, molecular docking was performed to study the interactions between these inhibitors and Aβ40. Docking showed that all inhibitors were bound to the similar region of Aβ40, and glycoside group formed hydrogen bonds with the pivotal residues Lys16. These results indicated that the glycoside groups could increase the inhibitory effects and reduce cytotoxicity. Glycosides have tremendous potential to be developed as an innovative type of aggregation inhibitor to control and treat neurodegenerative diseases.
研究领域:
神经生物学
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药理学
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生物化学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jianhang Li,Guanbin Gao,Xintong Tang,Meng Yu,Meng He,Taolei Sun
Chemical and physical properties of nanobio interface substantially affect the conformational transitions of adjacent biomolecules. Previous studies have reported the chiral effect and charge effect of nanobio interface on the misfolding, aggregation, and fibrillation of amyloid protein. However, the isomeric effect of nanobio interface on protein/peptides amyloidosis is still unclear. Here, three isomeric nanobio interfaces were designed and fabricated based on the same sized gold nanoclusters (AuNCs) modified with 4-mercaptobenzoic acid (p-MBA), 3-mercaptobenzoic acid (m-MBA), and 2-mercaptobenzoic acid (o-MBA). Then three isomeric AuNCs were employed as models to explore the isomeric effect on the misfolding, aggregation, and fibrillation of Aβ40 at nanobio interfaces. Site-specific replacement experiments on the basis of theoretical analysis revealed the possible mechanism of Aβ40 interacting with isomeric ligands of AuNCs at the nanobio interfaces. The distance and orientation of −COOH group from the surface of AuNCs can affect the electrostatic interaction between isomeric ligands and the positively charged residues (R5, K16, and K28) of Aβ40, which may affect the inhibition efficiency of isomeric AuNCs on protein amyloidosis. Actually, the amyloid fibrillation kinetics results together with atomic force microscope (AFM) images, dynamic light scattering (DLS) results and circular dichroism (CD) spectra indeed proved that all the three isomeric AuNCs could inhibit the misfolding, aggregation and fibrillation of Aβ40 in a dose-dependent manner, and the inhibition efficiency was definitely different from each other. The inhibition efficiency of o-MBA-AuNCs was higher than that of m-MBA-AuNCs and p-MBA-AuNCs at the same dosage. These results provide an insight for isomeric effect at nanobio interfaces, and open an avenue for structure-based nanodrug design target Alzheimer’s disease (AD) and even other protein conformational diseases.
研究领域:
生物化学
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纳米医学
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神经科学
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DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 20
·6579-6585
·
IF 3.978
Guanglei Lv,Yunze Xu,Jiajia Yang,Wenhui Li,Chunxia Li,Anyang Sun
Aberrant accumulation of Amyloid-β (Aβ) peptide is closely related to Alzheimer's disease. Thus, it is important to develop featured probes for the specific detection of Aβ species. Herein, we designed and synthesized a novel near-infrared fluorescent probe SDPY based on the D–π-A architecture for the detection of Aβ aggregates. The probe SDPY displayed higher affinity for Aβ40 aggregates over Aβ42 aggregates in solution (Kd = 164 nM vs. 2.1 μM). In addition, SDPY showed excellent anti-interference against a wide range of other substances. Furthermore, SDPY was capable of labeling Aβ40 aggregates better than Aβ42 aggregates in the brain sections of AD transgenic mouse models.
研究领域:
神经科学
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化学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Yana Zhao,Xin Li,Yuan Yang,Shihui Si,Chunyan Deng,Huiyun Wu
β-amyloid 1–40 oligomers (Aβ 40 O) is considered to be one of the important biomarkers for the diagnosis and treatment of Alzheimer's disease (AD). To explore a method with excellent performance is favorable for measuring the low concentration of Aβ 40 O in AD patients. Here, we developed a simple and fast method with a double stranded DNA (dsDNA)/graphene oxide (GO) based sensor, which was a fluorescent probe for a highly sensitive detection of Aβ 40 O down to 0.1 nM with a linear detectable range from 0.1 nM to 40 nM. The proposed sensor effectively reduced non-specific adsorption and improved the specificity of detection because of the covalent conjugation of a binding DNA (bDNA) containing Aβ 40 O-targeting aptamer (Apt Aβ ) onto GO surface, as well as the optimization of the number of mismatch base pairs of dsDNA. Moreover, AD patients and healthy persons were distinguished by this present method. All advantages of this method are exactly what the clinical detection of AD biomarkers need. This novel aptasensor might pave a way towards the early diagnosis of AD.
研究领域:
生物传感器
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神经科学
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分子诊断
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DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 44
·期 2
·618-633
·
IF 5.104
Qi Zhangyang,Wu Meihao,Fu Yun,Huang Tengfei,Wang Tingting,Sun Yanjie,Feng Zhibo,Li Changzheng
Background/Aims: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. Methods: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. Results: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin’s ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association constants for free P-curcumin and curcumin were 7.66 × 104 M-1 and 7.61 × 105 M-1, respectively. In the liposome-trapped state, the association constants were 3.71 × 105 M-1 for P-curcumin and 1.44× 106 M-1 for curcumin. With this data, the thermodynamic constants of P-curcumin association with soluble Aβ (ΔH, ΔS, and ΔG) were also determined. Conclusion: Cultivated curcumin weakened the direct interaction between Aβ and cell membranes and showed greater neuroprotective effects against Aβ insult than free curcumin
研究领域:
神经科学
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药理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Ximei Hu,Xiaoqi Chen,Jinlan Li,Jiawei Zhou,Xiaohua Zhu,Meiling Liu,Ying Liu,Youyu Zhang,Yang Liu
Amyloid-beta peptide (Aβ) is considered a promising biomarker for the diagnosis of Alzheimer’s disease (AD). Herein, we developed an anti-fouling photoelectrochemical (PEC) immunosensor for sensitive Aβ40 detection based on Z-scheme heterojunction poly (3,4-ethylenedioxythiophene) (PEDOT)/ZnIn 2 S 4 and zwitterionic peptide. Due to the excellent electrical conductivity of PEDOT, the Z-scheme PEDOT/ZnIn 2 S 4 heterojunction exhibited a high photocurrent response, which can promote the separation and transfer of photogenerated electron/hole pairs. The zwitterionic peptide with hydrophilicity and electrical neutrality was used as a blocking agent to reduce nonspecific adsorption. The proposed PEC immunosensor showed outstanding performance for Aβ40 with high selectivity, stability, wide liner range (from 10 pg mL −1 to 5 ng mL −1 ), and a low detection limit (4.7 pg mL −1 ). Moreover, the integration strategy of heterojunction with zwitterionic peptide provides a promising way for protein detection in practical applications.
研究领域:
生物医学工程
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分析化学
·
神经退行性疾病研究
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Yuemei Duan,Jia Chen,Yan Jin,Qiuyun Tu,Shuhui Wang,Juan Xiang
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly. Abnormal aggregates of both β-amyloid peptide (Aβ) subtypes, Aβ42 and Aβ40, are the typical neuropathology hallmarks of AD. However, because of the lack of specific recognition elements such as an antibody and aptamer, it is difficult to differentiate and determine the oligomers of Aβ42 and Aβ40 in clinic. In this paper, we developed a planar bilayer lipid membrane (BLM)-based electrochemical biosensor. According to the dynamic differences on oligomer-induced BLM damage, both low-mass, soluble oligomers of Aβ42 and Aβ40 (L-Aβ42O and L-Aβ40O) were measured in turn by electrochemical impedance spectroscopy. The BLM was supported by a porous 11-mercaptoundecanoic acid layer on a gold electrode, which amplified the impedance signal corresponding to the membrane damage and improved the detection sensitivity. The weakly charged surface of the BLM ensured the low non-specific adsorption of coexisting proteins in cerebrospinal fluid (CSF). Using the electrochemical biosensor, L-Aβ42O was determined within 20 min, with a linear range from 5 to 500 pM and a detection limit of 3 pM. Meanwhile, L-Aβ40O was determined within 60 min, with a linear range from 60 pM to 6.0 nM and a detection limit of 26 pM. The recoveries in oligomer-spiked artificial CSF and human CSF samples confirmed the accuracy and applicability of this proposed method in clinic. This work provides an antibody-free, highly selective, and sensitive method for simultaneous detections of L-Aβ42O and L-Aβ40O in real CSF samples, which is significant for the early diagnosis and prognosis of AD.
研究领域:
神经科学
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Zhenzhen Yin,Shuhui Wang,Baochai Shen,Chunyan Deng,Qiuyun Tu,Yan Jin,Lu Shen,Bin Jiao,Juan Xiang
Phosphorylated proteins play important roles in the pathogenesis of Alzheimer’s disease (AD). The most abundant constituent in AD’s brain deposit is the amyloid-β40 peptide (Aβ40). Based on it, the degree of phosphorylated Aβ40 in body fluids (e.g., cerebrospinal fluid, CSF), which is defined by the ratio of phosphorylated Aβ40 to total Aβ40 (pAβ40/tAβ40), is anticipated to be an index for early diagnosis of AD. The major challenge in pAβ40/tAβ40 detection is the large concentration difference between two Aβ40 forms in the real samples, which usually requires multichannel equipment and complicated detection process. In this paper, we revealed the unexpected close affinities of the anti-Aβ40 antibody to Aβ40 (40.2 nM–1) and to pAβ40 (42.3 nM–1). Based on it, a convenient coimmunocapture and electrochemical quantitation of tAβ40 and pAβ40 was achieved on an anti-Aβ40 antibody immobilized Au electrode (anti-Aβ40/Au). Once Aβ40 and pAβ40 were synchronously captured on the anti-Aβ40/Au electrode, the tAβ40 levels in CSF samples were quantified with electrochemical impedance spectroscopy. With the signal amplification from Cd2+/Ti4+-functionalized titanium phosphate nanospheres (Cd2+/Ti4+@TiP) which was selective conjugated to pAβ40, concentrations of low abundant pAβ40 as low as 1 fM were readily measured by square wave voltammetry. Our results reveal that despite the concentrations of tAβ40 and pAβ40 fluctuate in each individual case, the concentration ratios of pAβ40/tAβ40 in CSF samples from AD patients are significant larger than those from healthy donors. It demonstrates that the degree of phosphorylated Aβ40 is hopeful to be an effective index for evaluating the AD progress and improving the accuracy of clinic AD diagnosis.
研究领域:
生物化学
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医学诊断
·
神经科学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2025
·
IF 9.1
Guolin Hong,Xiaoyi Chen,Yuanyuan Yang,Yuanshuokun Feng,Qingfei He,Lingjun Cheng,Jilai Liu,Zhenyu Lin,Jiaming Chen
The quantitative and ultrasensitive detection of amyloid-beta peptides Aβ40 in blood is considered as a powerful strategy for early screening of Alzheimer’s disease (AD). In this study, combining dual-aptamer recognition and magnetic-induced enrichment, a background-free surface-enhanced Raman scattering (SERS) platform had been developed for efficient Aβ40 detection. Au@Ag-4-ethynylaniline@Au nanoparticles (Au@Ag-4-EA@Au NPs) had been designed and modified on aptamer2 of Aβ40 to form Au@Ag@4-EA@Au-Apt2 (SERS probe). 4-EA functionalization enables the use of the Raman silent region (1800–2800 cm–1), thereby minimizing biological interference and avoiding spectral overlapping. The nanogap within gold and silver nanoshells serves as a strong plasmonic enhancer, significantly amplifying the Raman signal and improving detection sensitivity. Aptamer1 of Aβ40 was modified on a streptavidin-modified magnetic bead (SA-MB) to form SA-MB-Apt1 (capture probe). The presence of the target results in the formation of the sandwich structure of SA-MB-Apt1/Aβ40/Apt2-Au@Ag-4-EA@Au NPs. Two Aβ40-specific aptamers ensured precise biomarker recognition and quantification. Magnetic-induced assembly enriches Aβ40 molecules and generates abundant plasmonic “hot spots” through nanoparticle aggregation, resulting in signal amplification. The results demonstrate a remarkable limit of detection of 25 fM (S/N = 3), with a linear range from 10–1 to 104 pM. This SERS platform provides a robust tool for early AD diagnosis and demonstrates broad potential in clinical molecular diagnostics.
研究领域:
分析化学
·
生物化学
·
生物医学工程
·
纳米技术
·
神经科学
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产品关联
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2022
·
IF 5.76
Zhaorong Gai,Fang Li,Xiaoyan Yang
Human serum albumin (HSA) is a major interaction-partner of amyloid- β (A β ) peptide in the plasma and can modulate the aggregation of A β . In this work, an efficient smart electrochemiluminescence (ECL) sensing platform was applied to determine the ability of HSA to bind different A β 40 aggregate species. Specifically, HSA was firstly adopted as a linker and self-assembled on the gold electrode, A β peptide were subsequently anchored onto the HSA-modified electrode through the recognition by HSA. CdS quantum dots (CdS QDs) modified with A β 40 aptamer as the ECL substrate were then captured on the electrode via the specific coordination between A β 40 and the aptamer. The present ECL sensor showed different ECL response in the presence of A β 40 with different aggregation states. The ECL platform exhibited a signal-on response with the introduction of A β 40 monomer in a concentration-dependent manner from 10 fM to 0.1 nM. Furthermore, the inhibition effect of several phenols on the aggregation of A β 40 was also investigated. This work potentially provided a feasible strategy of sensing platforms for A β detection and further understanding of the mechanism by which HSA modulates the aggregation of A β .
研究领域:
分析化学
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生物化学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 1
·1-9
·
IF 5.833
Wang Danhua,Dai Yibei,Wang Xuchu,Yu Pan,Qu Shufang,Liu Zhenping,Cao Ying,Zhang Lingyu,Ping Ying,Liu Weiwei,Tao Zhihua
A rolling circle amplification chemiluminescence immunoassay (RCA-CLIA) was developed for precise quantitation of Aβ in plasma. Capture antibodies conjugated with magnetic beads and detection antibodies with collateral single-stranded DNA (ssDNA) were bound to Aβ42/Aβ40 antigens to form a typical double-antibody sandwich structure. The RCA reaction was triggered by the addition of ssDNA, which generated products with a large number of sites for the binding of acridinium ester (AE)–labeled detection probes, thereby realizing the purpose of the amplification. The RCA-CLIA method had higher sensitivity than conventional CLIA without loss of specificity. Under optimum conditions, the linear range of Aβ42 and Aβ40 detection was 3.9–140 pg/mL and 3.9–180 pg/mL, respectively, with corresponding low detection limits of 1.99 pg/mL and 3.14 pg/mL, respectively. Plasma Aβ42 and Aβ40 were detected in the blood of 21 AD patients and 22 healthy people, wherein this ratio could significantly distinguish AD patients from healthy individuals with a sensitivity of 90.48% and specificity of 63.64% for a cutoff value of 154. The Aβ42/Aβ40 ratio of plasma acts as an accurate indicator for AD diagnosis; therefore, detection of plasma Aβ using the RCA-CLIA exhibits great potential in noninvasive diagnosis and progressive assessment of AD.
研究领域:
医学诊断
·
神经退行性疾病
·
生物技术
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2018
·
IF 3.47
Rong-zu Nie,Mei-zhu Dang,Kai-kai Li,Jin-ming Peng,Jing Du,Meng-ying Zhang,Chun-mei Li
A-type EGCG dimer is a new proanthocyanidins dimer from persimmon fruits. In the present study, we firstly examined the effects of EGCG and A-type EGCG dimer on Aβ 40 -fibrillization, and then the detailed mechanisms behind the inhibitory effects of polyphenols on Aβ 40 amyloid fibrils formation were investigated by PICUP assay, ESI-MS, NMR and molecular docking. Our results confirmed that A-type EGCG dimer exhibited stronger inhibitory effect on the formation of Aβ 40 amyloid fibrils. We found that A-type EGCG dimer possessed more binding sites on Aβ 40 peptide than EGCG. Notably, compared with EGCG, A-type EGCG dimer could interact with more amino acid residues which possessed obvious aggregation-propensity. And our results also suggested that the hydrophobic interaction was the principal driving force to inhibit the formation of Aβ 40 amyloid fibrils by A-type EGCG dimer. We believed that our study could provide useful insights for the design of low-molecular weight inhibitors of Aβ aggregation.
研究领域:
药理学
·
神经科学
·
生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
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