CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jing Zhao,Shibo Cheng,Xin Wang,Ruilian Yu,Bin Du,Jiajun Tong,Yiwei Liu,Taiping Qing,Xiaofeng Liu
In different contexts of Alzheimer's disease (AD), specific criteria for detecting toxic soluble amyloid β (Aβ) oligomers are crucial: Early detection requires highly-sensitive and accurate technology, while assessing treatment efficacy requires qualitative analysis using predefined thresholds. However, traditional methods, particularly single signal output, struggle to fulfill these criteria. Here, we present a urease-mediated homogeneous dual-mode biosensor that combines colorimetry and field-effect transistor (FET) through dual-aptamer recognition for the analysis of Aβ oligomers. This approach overcomes the challenges associated with surface modification of FET biosensors, allowing for both qualitative on-site detection (at pM levels) and highly-sensitive quantitative analysis (at fM levels) of Aβ oligomers in undiluted samples. The dual-mode biosensor displayed excellent performance in fetal bovine serum (FBS), artificial cerebrospinal fluid (aCSF) and rabbit whole blood samples, achieving a high recovery rate ranging from 96.1 % to 101 % and a low relative standard deviation between 1.7 % and 5.1 % when detecting Aβ oligomers in undiluted samples. Furthermore, clinical tests of serum and plasma samples from AD patients and healthy individuals also verified the sensitivity and specificity of the proposed dual-mode biosensor, demonstrating its potential application in early screening and monitoring of AD treatment processes.
研究领域:
生物传感器
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神经退行性疾病
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分析化学
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生物医学工程
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阿尔茨海默病研究
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Wen-Qiao Qiu,Rong Pan,Yong Tang,Xiao-Gang Zhou,Jian-Ming Wu,Lu Yu,Betty Yuen-Kwan Law,Wei Ai,Chong-Lin Yu,Da-Lian Qin,An-Guo Wu
Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSP dose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSP could significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together, LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.
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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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2021
·Vol. 7
·期 1
·1-13
·
IF 5.241
Yang Xiu,Li Xu,Liu Le,Chen Yuan-Hao,You Yue,Gao Yin,Liu Yue-Ying,Yang Li,Tong Kun,Chen Di-Shi,Hao Jing-Ru,Sun Nan,Zhao Zi-Ming,Gao Can
Alzheimer’s disease (AD) is characterized by aberrant accumulation of extracellular β-amyloid (Aβ) peptides in the brain. Soluble Aβ oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both Aβ oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the Aβ burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture Aβ oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered Aβ1-42 aggregation and disaggregated Aβ1-42 assembly due to multivalent PA-Aβ. Pep63 effectively inhibited the binding between EphB2 and Aβ oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.
研究领域:
神经科学
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药理学
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分子生物学
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhong-hao Zhang,Ying-hong Pei,Zhi-hao Duan,Tao Gao,Shi-ling Feng,Zi-zhong Tang,Yang-er Chen,Sheng-lin Hu,Shu Yuan,Wei Wang,Xiao-rong Yan,Ya-ying Pu,Ming Yuan
Alzheimer's disease (AD) is prevalent in the elderly, with amyloid-β (Aβ) playing a critical role in its progression. Polysaccharides have garnered increasing attention due to their low toxicity and diverse applications in alleviating AD-like symptoms. However, the potential of ginger leaf polysaccharide in mitigating AD-like symptoms has been rarely investigated. In this study, we isolated a polysaccharide (GLP1) from ginger leaf and evaluated its efficacy and underlying mechanisms in alleviating AD-like symptoms using Caenorhabditis elegans and PC12 cells. GLP1 ameliorated AD-like symptoms in C. elegans , as evidenced by a 41.50 % increase in head thrashing frequency and an 87.13 % increase in body bending frequency. Furthermore, GLP1 mitigated cognitive decline by 76.51 %. Additionally, GLP1 enhanced the activity of acetylcholinesterase in C. elegans and maintained the integrity of neural system function. Moreover, GLP1 improved the survival rate of PC12 cells under Aβ induction by activating the Wnt/β-catenin pathway, which also resulted in a reduction in the release of inflammatory factors, specifically IL-1β by 21.15 %, IL-6 by 39.98 %, and TNF-α by 19.66 %. Notably, FITC-labeled GLP1 could be absorbed by PC12 cells. These compelling findings underscored the therapeutic potential of GLP1 in alleviating Aβ-induced AD-like symptoms and supported the advancement of ginger leaf resource utilization.
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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老年医学
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DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 31
·17389-17398
·
IF 2.936
Yunquan Zheng,Qisheng Pan,Liuda Mo,Wenyi Zhang,Yunjian Duan,Chengqun Chen,Haijun Chen,Yanghao Guo,Xianai Shi,Jianmin Yang
Alzheimer's disease (AD) is an extremely complex disease, characterized by several pathological features including oxidative stress and amyloid-β (Aβ) aggregation. Blockage of Aβ-induced injury has emerged as a potential therapeutic approach for AD. Our previous efforts resulted in the discovery of Monascus pigment rubropunctatin derivative FZU-H with potential neuroprotective effects. This novel lead compound significantly diminishes toxicity induced by Aβ(1-42) in Neuro-2A cells. Our further mechanism investigation revealed that FZU-H inhibited Aβ(1-42)-induced caspase-3 protein activation and the loss of mitochondrial membrane potential. In addition, treatment of FZU-H was proven to attenuate Aβ(1-42)-induced cell redox imbalance and Tau hyperphosphorylation which caused by okadaic acid in Neuro-2A cells. These results indicated that FZU-H shows promising neuroprotective effects for AD.
研究领域:
神经科学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Liu Ni,Yang Changwen,Liang Xiaohan,Cao Kai,Xie Jun,Luo Qingming,Luo Haiming
Background Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aβ burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment.Methods We investigated the feasibility of intranasal delivery of MSNs-Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice.Results Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium. After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aβ burden but also improved olfactory sensitivity in APP/PS1 mice.Conclusion sThese findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.
研究领域:
神经科学
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药学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Small Structures
·
2024
·
IF 13.9
Tao Cheng,Peifen Lu,Yixi Dong,Jiabao Yu,Gang Wang,Jianwei Jiao,Peng Miao,Jin Jiao
Herein, a sequentially responsive peptide DNA bilingual nanobiosensor is developed, which allows integrated quantification of amyloid signaling pathway. In this system, upstream beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protease and downstream Aβ oligomer (AβO) are designed as two inputs for the AND DNA logic gate. In the existence of both inputs, peptide substrate with aptamer can be sequentially cleaved, reporting electrochemical and fluorescence dual-mode outputs. In comparison with conventional single protease activity assay based on peptide nanotechnology, this strategy permits accurate diagnosis of Alzheimer's disease (AD) from normal subjects. More importantly, it can achieve distinguished diagnosis between AD and type 2 diabetes mellitus patients. This bilingual nanobiosensor is successfully applied to detect BACE1 (1–100 U mL −1 ) and AβO (5–1000 pg mL −1 ) with limit of detections as low as 0.10 U mL −1 and 0.76 pg mL −1 , respectively. Furthermore, this strategy inspires advanced nanobiosensors to target the activation of other signaling pathways, which are potential tools for future biology and medicine investigation.
研究领域:
纳米技术
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生物化学
·
分子生物学
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诊断学
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神经退行性疾病
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产品关联
DOI
高影响因子
Oncotarget
·
2017
·
IF 5.168
Na Huang,Shuai Lu,Xiao-Ge Liu,Jie Zhu,Yu-Jiong Wang,Rui-Tian Liu
Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.
研究领域:
神经科学
·
药理学
·
纳米技术
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·Vol. 2021
·期 1
·9966223
·
IF 6.543
Weizhang Jia,Qina Su,Qiong Cheng,Qiong Peng,Aimin Qiao,Xiongming Luo,Jing Zhang,Ying Wang
Palmatine is a naturally occurring isoquinoline alkaloid that has been reported to display neuroprotective effects against amyloid- β - (A β -) induced neurotoxicity. However, the mechanisms underlying the neuroprotective activities of palmatine remain poorly characterized in vivo . We employed transgenic Caenorhabditis elegans models containing human A β 1-42 to investigate the effects and possible mechanisms of palmatine-mediated neuroprotection. Treatment with palmatine significantly delayed the paralytic process and reduced the elevated reactive oxygen species levels in A β -transgenic C. elegans . In addition, it increased oxidative stress resistance without affecting the lifespan of wild-type C. elegans . Pathway analysis suggested that the differentially expressed genes were related mainly to aging, detoxification, and lipid metabolism. Real-time PCR indicated that resistance-related genes such as sod-3 and shsp were significantly upregulated, while the lipid metabolism-related gene fat-5 was downregulated. Further studies demonstrated that the inhibitory effects of palmatine on A β toxicity were attributable to the free radical-scavenging capacity and that the upregulated expression of resistance-related genes, especially shsp , whose expression was regulated by HSF-1, played crucial roles in protecting cells from A β -induced toxicity. The research showed that there were significantly fewer A β deposits in transgenic CL2006 nematodes treated with palmatine than in control nematodes. In addition, our study found that A β -induced toxicity was accompanied by dysregulation of lipid metabolism, leading to excessive fat accumulation in A β -transgenic CL4176 nematodes. The alleviation of lipid disorder by palmatine should be attributed not only to the reduction in fat synthesis but also to the inhibition of A β aggregation and toxicity, which jointly maintained metabolic homeostasis. This study provides new insights into the in vivo neuroprotective effects of palmatine against A β aggregation and toxicity and provides valuable targets for the prevention and treatment of AD.
研究领域:
神经科学
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分子生物学
·
药理学
·
遗传学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Xueyan Yan,Yixin Pan,Liang Ji,Jinyu Gu,Yuanyuan Hu,Yi Xia,Chenglin Li,Xinguang Zhou,Dongzhi Yang,Yanyan Yu
In view of the close association of β-amyloid oligomers (AβO) with the clinical development of Alzheimer’s disease (AD) symptoms, it is urgent to design a promising sensing and therapeutic strategy that can target AβO for preventing or delaying the onset of AD. Herein, a core–shell nanocomposite CeONP-Res-PCM@ZIF-8/polydopamine (PDA) was synthesized through an in situ encapsulated strategy, in which resveratrol (Res), ceria nanoparticles (CeONPs), and PCM (tetradecanol) were embedded into the ZIF-8/PDA matrix via a water-based mild approach. Using the AβO aptamer, the ability of CeONP-Res-PCM@ZIF-8/PDA/Apt as the fluorescent sensing platform for AβO detection and intracellular imaging was demonstrated. The nanocomposite was high in Res loading (27.5%) and could be activated to release the encapsulated Res upon illumination with NIR through PCM regulation. Moreover, due to the synergetic interactions of PDA, CeONPs, and Res in one system, CeONP-Res-PCM@ZIF-8/PDA/Apt nanocomposites exhibited multifunctional effects on inhibiting Aβ aggregation, degrading Aβ fibrils, and alleviating Aβ-induced oxidative stress and neural apoptosis. These therapeutic effects could be enhanced under NIR irradiation by virtue of the excellent photothermal property of PDA. As far as we know, there is no report of using ZIF-8-based materials for simultaneous sensing and therapeutic applications. This work boosted the development of multifunctional nanoagents for biomedical research studies.
研究领域:
纳米技术
·
生物医学工程
·
神经科学
·
材料科学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Changjiang Li,Na Wang,Guodong Zheng,Licong Yang
Alzheimer’s disease (AD) is a neurodegenerative disease associated with amyloid-β (Aβ) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aβ aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood–brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aβ and decreasing Aβ aggregation, effectively inhibiting Aβ deposition in the hippocampus; (2) decreasing Aβ-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aβ-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.
研究领域:
神经科学
·
药理学
·
纳米技术
·
生物化学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Baojun Sun,Xun Zhang,Huan Chen,Xinxin Wang,Yujiao Lou,Linna Han,Qun Huang,Shaofeng Wei,Yun Ma
Taurine, a semi-essential amino acid enriched in animal-derived foods, is well established for its roles in improving exercise capacity and reducing fatigue. However, its potential protective effects in the brain, especially against mitochondrial dysfunction associated with Aβ pathology, remain poorly understood. This study found that taurine supplementation significantly improved spatial learning and memory in the Morris water maze (MWM) of healthy Sprague-Dawley (SD) rats. To explore the underlying mechanism, we examined taurine's effects on Aβ-treated hippocampal neurons, where it restored mitochondrial membrane potential and preserved the ATP/ADP ratio. Untargeted metabolomic analysis revealed that taurine reactivated the tricarboxylic acid (TCA) cycle and enhanced its own biosynthetic pathway. Taurine activated the AMP-activated protein kinase (AMPK) pathway and increased expression of downstream factors involved in mitochondrial biogenesis, including PGC-1α, TFAM, NRF1, NRF2, MEF2α, and SDH. Collectively, these findings demonstrate that taurine improves spatial learning and memory in healthy rats and attenuates Aβ-induced mitochondrial dysfunction and metabolic disturbances in hippocampal neurons. These findings support the potential role of taurine as a food-derived bioactive compound for maintaining neuronal health.
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DOI
高影响因子
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