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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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Hui Liu,Xueli Yuan,Tao Liu,Wei Zhang,Heng Dong,Zhenyu Chu
Amyloid beta-protein (AβA β ) is a main hallmark of Alzheimer's disease (AD), and a low amount of Aβ protein accumulation appears to be a potential marker for AD. Here, an electrochemical DNA biosensor based on polyamide/polyaniline carbon nanotubes (PA/PANI-CNTs) is developed with the aim of diagnosing AD early using a simple, low-cost, and accessible method to rapidly detect Aβ42 in human blood. Electrospun PA nanofibers served as the skeleton for the successive in situ deposition of PANI and CNTs, which contribute both high conductivity and abundant binding sites for the Aβ42 aptamers. After the aptamers are immobilized, this aptasensor exhibits precise and specific detection of Aβ42 in human blood within only 4 min with an extremely fast response rate, lower detection limit, and excellent linear detection range. These findings make a significant contribution to advancing the development of serum-based detection techniques for Aβ42, thereby paving the way for improved diagnostic capabilities in the field of AD.
研究领域:
医学诊断
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生物传感技术
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神经科学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Wang Zixun,Wang Yinan,Bi Caili,Zhou Yangfan,Zhu Tao,Jin Xing
In this study, a highly sensitive surface-enhanced Raman scattering-chiral anisotropy (SERS-ChA)-based microarray chip was fabricated for the quantitative analysis of β-amyloid protein (Aβ42) in Alzheimer’s disease (AD). To construct the chip, D-type chiral gold nanoparticles (CG NPs) were employed as the plasmonic substrate, creating uniformly distributed and densely packed hotspots. The localized chiral plasmonic electromagnetic fields generated at the chiral hotspots provide a chirality-dependent enhancement preference for Aβ42 molecules, leading to significant enhancement of their characteristic Raman signals and thereby improving the sensitivity and specificity of detection. Within the linear range of 100 fg/mL to 10 ng/mL, the logarithmic concentration of Aβ42 showed a strong linear correlation with the SERS signal intensity at 1322 cm − 1 . The linear regression equation was y = 1529.72x + 2748.38 (R 2 = 0.9871), and the limit of detection reached the fg/mL level. This microarray chip features low sample consumption, high sensitivity, and high throughput, demonstrating considerable potential for non-invasive early diagnosis of AD. Graphical
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Ma Liang,Zheng Jiaojiao,Chen Huijing,Zeng Xia,Wang Shilin,Yang Chen,Li Xi,Xiao Yushuo,Zheng Ling,Chen Hong,Huang Kun
The toxic aggregates of amyloid beta (Aβ) disrupt the cell membrane, induce oxidative stress and mitochondrial dysfunction, and eventually lead to Alzheimer’s disease (AD). Intervening with this cytotoxic aggregation process has been suggested as a potential therapeutic approach for AD and other protein misfolding diseases. Traditional Chinese Medicine (TCM) has been used to treat AD and related cognitive impairment for centuries with obvious efficacy. Extracts or active ingredients of TCMs have been reported to inhibit the aggregation and cytotoxicity of Aβ. However, there is a lack of systematic research on the anti-Aβ aggregation effects of TCM components. In this study, we performed a systematic screening to identify the active ingredients of TCM against the cytotoxic aggregation of Aβ42. Through a literature and database survey, we selected 19 TCM herbals frequently used in the treatment of AD, from which 76 major active chemicals without known anti-amyloid effects were further screened. This took place through two rounds of MTT-based screening detection of the cytotoxicity of these chemicals and their effects on Aβ42-induced cytotoxicity, respectively. Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and sinapic acid (SA) were found to be less toxic, and they inhibited the cytotoxicity of Aβ42. Further studies demonstrated that TSG and SA concentration-dependently attenuated the amyloidosis and membrane disruption ability of Aβ42. Thus, we identified two novel chemicals (TSG and SA) against the cytotoxic aggregation of Aβ42. Nonetheless, further exploration of their therapeutic potential is warranted.
研究领域:
神经科学
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药理学
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传统中药
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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
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神经退行性疾病
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生物技术
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DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2025
·
IF 4.5
Xue Kong,Zimei Yu,Qinghua Sun,Yan Liu,Zheng-Zhi Yin
Monitoring beta-amyloid 1 – 42 (Aβ 42 ) is vital and challenging, which is a typical biomarker of Alzheimer's disease. Here, a novel electrochemical microbiosensor is developed to detect Aβ 42 on an acupuncture needle. Hemin is well known for its characteristics, including its ability to self-assemble on single-walled carbon nanotube (SWCNT), the molecular interaction with Aβ 42 , and the intrinsic electroactive signal. These properties are exploited to anchor and respond to Aβ 42 after integrating a molecularly imprinted surface polymer (SMIP). The SMIP layer of polydopamine/poly (ionic liquid) can be prepared by electropolymerization on an acupuncture needle microelectrode (ANME), which undergoes growth and formation of a polymeric structure around the anchored Aβ 42 . Interestingly, the imprinted cavities express a fluent signal of built-in hemin after eluting the templates, and show a highly selective and sensitive hindrance response for the recombined Aβ 42 . Under optimized conditions, the microbiosensor displays a linear range of 100 to 1 × 10 10 fM with a limit of detection of 0.05 fM. There are development and advances for the discipline of electroanalysis after comparing the technique and important indicators with the electrochemical biosensors reported of Aβ 42 . The microbiosensor also exhibited excellent selectivity, good stability, and reproducibility, which was effectively used to detect Aβ 42 in real spiked samples. The improved behavior of the developed microbiosensor can be attributed to its superficial highly matched imprinted cavities, built-in hemin label, and electronic barrier without signal of the nonimprinted surface to outside molecules. This microbiosensor has a scientific and reference value for directly sensing non-electroactive biomarkers, functionalizing microelectrodes, and electron transport cavities. It would also be amazing if this new microbiosensor could combine with the unclear and magical property of acupuncture in the treatment of neurological disorders.
研究领域:
电分析
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生物传感器
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神经化学
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分析化学
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纳米技术
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分子印迹
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Ke-Lin Chen,Ling Gan,Zhen-Hua Wu,Jin-Fang Qin,Wen-Xia Liao,Huang Tang
A series of 4- substituted sampangine derivatives (4-aminoalkylaminosampangine Ar–NH(CH 2 ) n NR 1 R 2 ) has been designed, synthesized, and tested for their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-myloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 secretion levels. Moreover, most of the synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.
研究领域:
药理学
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神经科学
·
化学
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DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Shicai Wang,Ruijun Deng,Zhiya Chen,Lili Huang,Yang Song,Dan Yuan,Yu Li,Haonan Liu,Fan Yang,Beiyuan Fan,Yun Xu,Zijian Zhao,Yanzhao Li,Yan Zhang
Alzheimer’s disease (AD) is the most common cause of dementia in older people. However, diagnosing AD through noncognitive methods, such as invasive cerebrospinal fluid sampling or radioactive positron emission tomography, has limited applications. Herein, the femtomolar levels of AD biomarkers amyloid β 40 (Aβ40), amyloid β 42 (Aβ42), phosphorylated tau 181 (P-tau181), phosphorylated tau 217 (P-tau217), and neurofilament light chain (NfL) were determined in human plasma in multicenter clinical cohorts using an ultrasensitive graphene field-effect transistor sensor. A machine-learning algorithm was also used to assemble these plasma biomarkers and optimize their performance in discriminating individual stages of Alzheimer’s dementia progression. The “composite-info” biomarker panel, which combines these biomarkers and clinical information, considerably improved the staging performance in AD progression. It achieved an area under the curve of >0.94 in the receiver operator characteristic (ROC) curve. In addition, the panel demonstrated an advantage in the individual-based stage assessment compared with that of the Mini-Mental State Examination/Montreal Cognitive Assessment and nuclear magnetic resonance imaging. This study provides a composite biomarker panel for the screening and early diagnosis of AD using a rapid detection system.
研究领域:
神经学
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生物标志物研究
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医学诊断
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机器学习
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石墨烯技术
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2018
·
IF 3.929
Juan Wang,Wei Li,Jingfang Qin,Li Wang,Shenqi Wei,Huang Tang
A series of 6-substituted azaanthraquinone derivatives have been designed, synthesized, and their anti-inflammatory activities, antiaggregation effects on β-amyloid proteins, anticholinesterase and neuroprotective activity were tested. The new derivatives strongly suppressed NO and iNOS production and modulate the production of cytokines by decreasing TNF-a, IL-1β and IL-6 formation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Meanwhile, the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human b-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 secretion levels. Moreover, the derivatives exhibited moderate inhibitory potency toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Further investigations indicated that compound 7b could attenuate H 2 O 2 -induced neurotoxicity toward SH-SY5Y neuroblastoma cells and half of the synthetic compounds were predicted to be able to cross the blood–brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Taken together, azaanthraquinone derivatives targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD.
研究领域:
药理学
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神经科学
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药物化学
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DOI
PubMed
高影响因子
Journal of Analysis and Testing
·
2025
·
IF 7
Lv Yubing,Zhou Yanli,Lv Chaoran,Wang Mengyao,Sheng Nan,Lin Yuanyuan,Wang Cancan,Xu Maotian,Zhang Jing,Yan Mei
In view of the importance of quantification of beta-amyloid (Aβ), an “aptamer -target- peptide” sandwich electrochemical biosensor to assay Aβ42 was fabricated by using gold–palladium bimetallic nanoparticles covalent organic framework-carbon cloth (Au–Pd@COF TTF-Thi -CC) and prion protein (PrP C ) labeled with horseradish peroxidase (HRP) nanocomposites. The concentration of Aβ42 showed a positive correlation with the peak current resulting from the oxidation of hydroquinone (HQ) by HRP. In contrast, the reference current signal from thionin (Thi), derived from covalent organic framework (COF), showed a negative correlation. The current response of the electrochemical biosensor was proportional to the Aβ concentrations ranging from 0.01 to 2.5 nM with a detection limit (LOD) of 2.17 fM ( S / N = 3). The sensitivity of the sandwich electrochemical biosensor could be primarily amplified based on the substrates of Au–Pd@COF TTF-Thi -CC. The AuNPs and PdNPs not only facilitated the bonding of the linker based on the Au–S bond but also improved the performance of COF TTF-Thi -CC. Secondary sensitivity amplification of the biosensor could be achieved by using PrP C -labeled HRP to catalyze hydroquinone in solution. Furthermore, the biosensor showed excellent selectivity, anti-interference performance, and stability. The Aβ concentrations in cerebrospinal fluid (CSF) were successfully evaluated using the constructed biosensor. This assay provides a potential tool for early-stage Alzheimer's disease diagnosis.
研究领域:
生物传感器
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纳米技术
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神经化学
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电化学
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分析化学
·
阿尔茨海默病研究
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高影响因子
BIOFACTORS
·
2021
·Vol. 47
·期 4
·587-599
·
IF 6.113
Ninghua Wu,Wu Liu,Jiawen Wang,Yanqi Han,Yu Ye,Xiufen Liu,Yuandong Yu,Qingjie Chen,Yongfen Bao,Chao Liu
IR (insulin resistance) in diabetic brain gave rise to the generation of toxic factor Aβ42 and axon collapse which were the marker of AD (Alzheimer's disease)-like lesions in the circumstance of diabetes mellitus. But the underling molecular mechanism was not clear. Chronic HGHI (high glucose and high insulin) exposure accelerates IR has been reported in type II diabetes models. Berberine has been shown to promising effect for IR in vitro and in vivo. This study demonstrates the protective effect and the underlying mechanism of berberine on HGHI-induced IR. HGHI-induced cells were used to mimic the hyperinsulinemia resulting in IR. Berberine was used to uncover the mechanisms for the treatment of hyperinsulinemia in IR model. Morris water maze (MWM), PET imaging, CCK8 assay, ELISA assay, glucose kits, microscopy, and western blot analysis were performed to evaluate the protective effects of berberine. Berberine-improved HGHI-induced IR was correlated with the increase of glucose application in neurons. Meanwhile, the expressions of Pi3K, as well as GLUT3, PKCε, and APP were downregulated in the model, while p-IRS Ser307 was upregulated compared with Normal group. Fortunately, these scenes were reversed by berberine administration. Furthermore, berberine decreased GSK3β Y216 expressions, inhibited the production of oligomer Aβ42 and extended neuronal axon. The monomeric berberine treatment improves IR that may be involved in glucose effective application, rectifying the related proteins of the aberrant insulin pathway. Additionally, it suppressed the generation of Aβ42 and ameliorated neuron axon damage. Finally, berberine improves DM (diabetes mellitus)-induced cognitive impairment.
研究领域:
药理学
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神经科学
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糖尿病学
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分子生物学
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PubMed
高影响因子
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