ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Chengjie Duan,Wenting Cheng,Yanheng Yao,Dayong Li,Zhongyun Wang,Yang Xiang
Aptamer-based methods have attracted increasing interest due to flexible engineering, but their generality is limited by the heterogeneity of signal transduction mechanisms. Given the fact that nonlinear and large molecules are more likely to make the nanosurface overloaded, we investigated a novel signal transduction process to extend the application of aptasensors. In this work, an aptamer complementary element (ACE) is designed with a primer region to serve as the signal probe, which can fully hybridize with an aptamer and be separated by magnetic beads (MBs). Upon target binding, the formed aptamer/target complex is much larger than the linear aptamer/ACE-primer dimer, causing overload of MBs on account of steric hindrance. An extra aptamer/ACE-primer can escape from the surface to the supernatant, which can be amplified by a catalytic hairpin assembly (CHA) circle. The size-dependent signal transduction and the modular design endow the method with high generality and flexibility for protein analysis. The proposed aptasensor was successfully applied to the detection of tau proteins ranging from 0.5 to 1000 ng mL–1 with a limit of detection (LOD) as low as 0.254 ng mL–1. The recovery tests in both human serum and cerebra spinal fluid confirmed the high accuracy and stability. Furthermore, a successful distinction was made between AD patients and healthy controls by the method, suggesting the possible applicability for practical analysis of tau proteins.
研究领域:
生物化学
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分子诊断
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分析化学
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DOI
PubMed
高影响因子
ACS Nano
·
2018
·
IF 13.709
Qing Chen,Yang Du,Kai Zhang,Zeyu Liang,Jinquan Li,Hao Yu,Rong Ren,Jin Feng,Zhiming Jin,Fangyuan Li,Jihong Sun,Min Zhou,Qinggang He,Xiaolian Sun,Hong Zhang,Mei Tian,Daishun Ling
Alzheimer’s disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-β (Aβ) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aβ deposition and cognition, as well as the failures of Phase III clinical trial on Aβ targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The memory deficits of AD rats are significantly rescued upon treatment with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated tau-targeted multifunctional nanocomposites could be a promising therapeutic candidate for Alzheimer’s disease.
研究领域:
神经科学
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药学
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纳米技术
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治疗学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Neuroscience
·
2020
·
IF 4.057
He Zhijun,Han Shuangxue,Zhu Huazhang,Hu Xia,Li Xiaoqian,Hou Chaofan,Wu Chong,Xie Qingguo,Li Nan,Du Xiubo,Ni Jiazuan,Liu Qiong
Alzheimer’s disease (AD) is a widely distributed neurodegenerative disease characterized clinically by cognitive deficits and pathologically by formation of amyloid-β (Aβ) plaque and neurofibrillary tangles (NFTs) in the brain. Vanadium is a biological trace element that has a function to mimic insulin for diabetes. Bis(ethylmaltolato) oxidovanadium (IV) (BEOV) has been reported to have a hypoglycemic property, but its effect on AD remains unclear. In this study, BEOV was supplemented at doses of 0.2 and 1.0 mmol/L to the AD model mice APPSwe/PS1dE9 for 3 months. The results showed that BEOV substantially ameliorated glucose metabolic disorder as well as synaptic and behavioral deficits of the AD mice. Further investigation revealed that BEOV significantly reduced Aβ generation by increasing the expression of peroxisome proliferator-activated receptor gamma and insulin-degrading enzyme and by decreasing β-secretase 1 in the hippocampus and cortex of AD mice. BEOV also reduced tau hyperphosphorylation by inhibiting protein tyrosine phosphatase-1B and regulating the pathway of insulin receptor/insulin receptor substrate-1/protein kinase B/glycogen synthase kinase 3 beta. Furthermore, BEOV could enhance autophagolysosomal fusion and restore autophagic flux to increase the clearance of Aβ deposits and phosphorylated tau in the brains of AD mice. Collectively, the present study provides solid data for revealing the function and mechanism of BEOV on AD pathology.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Haolin Xiao,Chenghao Liu,Hanwen Ren,Shanshan Wei,Feijun Zhao,Liangli Cao,Zhencheng Chen
The advancement of Alzheimer’s disease (AD) is directly correlated to the phosphorylation damage of Tau protein (Tau-441), which is considered the most reliable indicator for early detection of AD. Nevertheless, the concentration of Tau-441 in human serum remains considerably low. To address this issue, a paper-based fluorescence immunosensor based on internal filter effect (IFE) was developed for the detection Tau-441. The microfluidic paper-based channel was prepared and modified with a gold layer to attach primary antibodies and increase the sensitivity of the sensor. All at once, Au@CeO 2 nanorods was employed as a fluorescence probe to hydrolyze p-nitrophenyl phosphate ( pNPP ), which generates hydrolyzed product p-nitrophenol (PNP) can reduce or quench the fluorescence intensity of N-doped graphene quantum dots (NGQDs). The immunosensor was designed to detect an increase in the amount of Tau-441 collected as the fluorescence intensity of NGQDs decreased. The developed sensor demonstrated satisfactory results in clinical serum samples, offering a promising concept for an immunoassay tagged with nanozymes for early detection of AD. Overall, this microfluidic paper-based fluorescent immunosensor has the potential to improve early diagnosis of AD.
研究领域:
生物医学工程
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医学诊断
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纳米技术
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产品关联
DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
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IF 8.2
Xiaoyu Fu,Jing Han,Yu Xia,Wei Wang,Ya Wen,Boning Zhang,Xue Zhang,Xinyu Wang,Shengnan Han,Chenggang Zhang
Alzheimer's disease (AD) incidence is rising with no effective treatments. Eleutheroside B (EB) has neuroprotective potential, but its therapeutic effects and mechanisms in AD are unclear. This study investigated EB's effects on AD pathologies and elucidated its underlying mechanisms using a transgenic Caenorhabditis elegans ( C. elegans ) model. We found that EB could ameliorate cognitive impairment, locomotor dysfunction, and shortened lifespan induced by amyloid-β(Aβ) and Tau aggregation in C. elegans , and reduce the relative expression levels of Aβ, Tau, and phosphorylated Tau (p-Tau) proteins. EB significantly improved the health status and anti-aging capacity of the worms, as evidenced by prolonged healthspan, elevated pharyngeal pumping rate and body bend frequency, and increased body length and width. Notably, EB exhibited no observable toxicity even at high-dose administration. Furthermore, EB activated key antioxidant transcription factors skn-1 , daf-16 , and hsf-1 ; it also increased the expression levels of antioxidant enzymes superoxide dismutase-3(SOD-3) and glutathione S-transferase 4(GST-4), decreased reactive oxygen species (ROS) levels, and elevated the expression of heat shock proteins Hsp-4 and Hsp-6. EB also reduced the accumulation of p62/SQST-1 protein, promoted the colocalization of lgg-1::GFP with lysosomes, and increased the relative mRNA expression of autophagy-related genes aak-2 , unc-51 , bec-1 , vps-34 , and lgg-1 . After targeted knockdown of these genes, the protective effects of EB against AD-related pathologies were abolished. Our findings demonstrate that EB exhibits anti-aging properties and potential for ameliorating AD, which is likely mediated via antioxidative activities and autophagy induction.
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Zhao-huan Zhang,Junjie Hu,Han Zhu,Qiang Chen,Kwangnak Koh,Hongxia Chen,Xiao-hui Xu
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disease. Plasma total phosphorylated tau (P-tau) with multi-phosphorylation sites is a potentially efficient biomarker for the diagnosis and prognosis of AD. Single phosphorylation site recognition methods lead to the false positive detection of P-tau and decrease the accuracy of AD analysis. In this work, a simple and precise electrochemical immunoassay was developed for the specific detection of P-tau. Calixarene derivative ProLinker was utilized to orient Anti-tau onto the surface of gold electrode. ProLinker provide abundant binding sites for immobilized antibodies via host-guest recognitions and ensure Anti-tau activity through non-covalent interactions. Flower-shaped TiO 2 (F-TiO 2 ) forming coordination bonds with the phosphate group of phosphorylated protein were utilized as signal amplification tags to construct a simple sandwich assay for multiple phosphorylated sites sensing of P-tau. The combination of F-TiO 2 and Anti-tau ensured the bispecific and precise recognition of P-tau with a wide detection range (1–200 ng/mL) and a low detection of limit (1.774 pg/mL). With large specific surface area, high electron hinder ability, and great stability, F-TiO 2 as an amplification molecule can improve the performance of the immunosensor and produce sensitive signal changes according to the concentration of P-tau in the clinical samples. Hence, this P-tau immunoassay paves the way for the development of efficient detection tools for clinical diagnosis and monitoring.
研究领域:
生物医学工程
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神经科学
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诊断学
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2019
·Vol. 411
·期 20
·5277-5285
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IF 3.286
Chen Li,Lin Jianwei,Yi Jinquan,Weng Qinghua,Zhou Ying,Han Zhizhong,Li Chunyan,Chen Jinghua,Zhang Qian
Rapid, highly sensitive detection of tau protein and other neurodegenerative biomarkers remains a significant hurdle for diagnostic tests for Alzheimer's disease. In this work, we developed a novel tyrosinase (TYR)-induced tau aptamer–tau–tau antibody (anti-tau) sandwich fluorescence immunoassay to detect tau protein that used dopamine (DA)-functionalized CuInS 2 /ZnS quantum dots as the fluorophore. CuInS 2 /ZnS core/shell quantum dots with high luminescence, low toxicity, and excellent biocompatibility were successfully fabricated and decorated with DA through amide conjugation. Meanwhile, TYR was conjugated with anti-tau by a click reaction. When DA-functionalized CuInS 2 /ZnS quantum dots were added to the sandwich system, TYR catalyzed the transformation of DA to dopamine quinone, which acted as an effective electron acceptor and triggered fluorescence quenching. The fluorescence intensity of the immunoassay based on DA-functionalized CuInS 2 /ZnS quantum dots shows good performance in terms of linearity with the logarithm of tau protein concentration, with a linear concentration range from 10 pM to 200 nM. This work is the first to use a TYR-induced fluorescence immunoassay for the rapid detection of tau protein, paving a new way for the detection of disease biomarkers.
Graphical abstract
研究领域:
生物化学
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纳米技术
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神经科学
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诊断学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
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2025
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IF 2.6
Xiao-Han Ma,Hui Dai,Song-Yao Liu,Xiao-Na Liu,Jing Zhang,Xue-Lian Meng
Glutamate (Glu) excitotoxicity and amyloid-β (Aβ) deposition are significant factors in the occurrence and development of Alzheimer’s disease (AD). Dauricine and daurisoline are two alkaloid components of Menispermum dauricum DC . that have a protective effect on the nervous system. The protection of dauricine and daurisoline on Glu-injured PC12 cells and the protection dauricine on Aβ 25-35 -injured PC12 cells were investigated in this study. The results of the study demonstrated that on PC12 cells damaged by Glu (20 mM), dauricine and daurisoline (3 and 10 μM) increased the cell viability, reduced cell apoptosis, and enhanced mitochondrial membrane potential (MMP) levels. Dauricine and daurisoline can also reduce the levels of intracellular ROS and free Ca 2+ , and suppression the expression of CaM, p-CaMKII, and p-Tau in Glu-damaged PC12 cells. In addition, on PC12 cells damaged by Aβ 25-35 (30 μM), dauricine (3 and 10 μM) can also significantly increase the cell viability and MMP levels, inhibit cell apoptosis, reduce intracellular ROS and free Ca 2+ levels, and down-regulate protein expression of CaM, p-CaMKII, and p-Tau. This study demonstrates for the first time that dauricine and daurisoline may inhibit the excessive phosphorylation of Tau protein and subsequent cell apoptosis by suppressing the Ca 2+ -CaM/CaMKII pathway, thereby protecting PC12 cells damaged Glu or Aβ 25-35 in vitro . Dauricine and daurisoline have the potential to treat AD effectively and have further research value.
研究领域:
神经生物学
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药理学
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阿尔茨海默病研究
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Chen Chongyang,Liu Pan,Wang Jing,Yu Haitao,Zhang Zaijun,Liu Jianjun,Chen Xiao,Zhu Feiqi,Yang Xifei
Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of β-amyloid (Aβ) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. No effective therapy is available for this disease. In this study, we investigated the potential therapeutic effects of dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid, on AD, and found that DAU administration significantly improved cognitive impairments in 3xTg-AD mice by decreasing Aβ plaques and hyperphosphorylated tau and increasing the hippocampal ATP level. Proteomic and western blot analyses revealed that DAU treatment mainly modified the expression of proteins involved in mitochondrial energy metabolism, such as Aco2, Ndufs1, Cox5a, and SDHB, and that of synapse-related proteins such as Syn1 and Syn2. Pathway analysis revealed that DAU modulated the tricarboxylic acid cycle, synaptic vesicle cycle, glycolysis, and gluconeogenesis in 3xTg-AD mice. Our study suggests that DAU may be a potential drug for the treatment of AD.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-13
·
IF 4.6
Chakari-Khiavi Forough,Mirzaie Arezoo,Khalilzadeh Balal,Yousefi Hadi,Abolhasan Rozita,Kamrani Amin,Pourakbari Ramin,Shahpasand Koorosh,Yousefi Mehdi,Rashidi Mohammad-Reza
Alzheimer’s disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein ( cis -p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL −1 to 10 ng mL −1 and the low limit of detection (LOD) of 1 fg mL −1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening 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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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jiani Huang,Fei Wu,Wenzhao Cao,Yuhan Chen,Qiong Yao,Peili Cen,Jing Wang,Lu Hong,Xiaohui Zhang,Rui Zhou,Chentao Jin,Mei Tian,Hong Zhang,Yan Zhong
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder globally, with no effective treatment available yet. A crucial pathological hallmark of AD is the accumulation of hyperphosphorylated tau protein, which is deteriorated by reactive oxygen species (ROS) and neuroinflammation in AD progression. Thus, alleviation of ROS and inflammation has become a potential therapeutic strategy in many studies. Herein, we reported ultrasmall coordination polymer nanoparticles formed by ferric ions and gallic acid (Fe-GA CPNs), which owned antioxidant and anti-inflammation properties for AD therapeutics. The facilely prepared Fe-GA CPNs exhibited remarkable superoxide dismutase, peroxidase enzyme activity, and ROS eliminating ability with great water solubility, compared with gallic acid. We demonstrated that Fe-GA CPNs effectively relieved oxidative stress, ameliorated inflammation by downregulating TLR4/NF-κB and modulating microglial polarization towards anti-inflammation phenotype, and reduced hyperphosphorylated tau protein levels. Furthermore, Fe-GA CPNs treatment significantly improved cognitive function in tauopathy-induced AD rats, and achieved a neuroprotective effect against AD pathology. This study highlights the potential of coordination polymer nanoparticles as promising therapeutic candidates for AD and other tau-related neurodegenerative diseases.
研究领域:
神经退行性疾病
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纳米技术
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药理学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2021
·
IF 4.418
Yuan Hu,Danjing Yang,Ying Tu,Keke Chai,Lei Chu,Shuo Shi,Tianming Yao
A molecular inhibitor of tau protein aggregation offers an attractive therapeutic possibility as disease-modifying treatment of Alzheimer’s disease. However, the ineffectiveness as well as adjoint toxicity due to superficial understanding of the inhibition mechanism has hindered drug development. Conventional approaches for screening drug ligands rely on compatible docking with the well-defined structure of a protein receptor. Therefore, the design of tau aggregation inhibitors has been inevitably hindered by the unstructured, highly dynamic nature of the tau protein. This paper suggested a new strategy for reducing tau aggregation through a dynamic process of conformational isomerization. A group of glucose gallate derivatives were selected as tau aggregation inhibitors. These star-shaped molecules have a biocompatible glucose core surrounded by several gallic acid polyphenol arms, which can bind to peptide chains at different sites, probably through hydrogen bonds and π–π stacking. Theoretically, by elevating the saddle point on the potential energy surfaces (PES) of proteins, the barrier in the dynamic pathway of peptide isomerization, glucose gallates effectively inhibit tau aggregation through a dynamic mechanism. A tau cell model based on human neurons was constructed. For the first time, we confirmed that the moderate thermodynamic binding of the molecular ligand to the tau peptide chain can not only prevent the isomerization of the peptide chain leading to aggregation but also avoid toxicity resulting from the dissociation of tau from microtubules.
研究领域:
神经科学
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药物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）