JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Qiang-Ming Li,Hui-Hui Han,Dan-Dan Zang,Xue-Qiang Zha,An Zhou,Feng-Yun Zhang,Jian-Ping Luo
An amyloid-β (Aβ) fibril is a vital pathogenic factor of Alzheimer’s disease (AD). Aβ fibril disintegrators possess great potential to be developed into novel anti-AD agents. Here, a ligand fishing method was employed to rapidly discover Aβ42 fibril disintegrators from Ganoderma lucidum using Aβ42 fibril-immobilized magnetic beads, which led to the isolation of six Aβ42 fibril disintegrators including ganodermanontriol, ganoderic acid DM, ganoderiol F, ganoderol B, ganodermenonol, and ergosterol. Neuroprotective evaluation in vitro exhibited that these Aβ42 fibril disintegrators could significantly mitigate Aβ42-induced neurotoxicity. Among these six disintegrators, ergosterol and ganoderic acid DM with stronger protecting activity were further selected to evaluate their neuroprotective effect on AD in vivo. Results showed that ergosterol and ganoderic acid DM could significantly alleviate Aβ42-induced cognitive dysfunction and hippocampus neuron loss in vivo. Moreover, ergosterol and ganoderic acid DM could significantly inhibit Aβ42-induced neuron apoptosis and Nrf2-mediated neuron oxidative stress in vitro and in vivo.
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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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Honghe Xiao,Hongyan Li,Huipeng Song,Liang Kong,Xin Yan,Yan Li,Yan Deng,He Tai,Yutong Wu,Yingnan Ni,Wanyi Li,Jicong Chen,Jingxian Yang
Ethnopharmacological relevance According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as “forgetfulness” or “dementia”, and is mainly caused by “kidney essence deficiency” which ultimately induces “encephala reduction”. Therefore, herbal formulas possessing the efficacy of nourishing kidney essence or replenishing brain marrow are commonly served as effective strategies for AD treatment. Shenzao jiannao oral liquid (SZJN), a traditional Chinese preparation approved by the China Food and Drug Administration (CFDA), is used for the treatment of insomnia and mind fatigue at present for its efficacy of nourishing kidneys. In present study, we found that SZJN could improve cognitive function of AD-like mice. Aims of study This study aims to investigate the effects of SJZN on ameliorating cognitive deficits of AD-like mouse model, and to illuminate the underlying mechanisms from the perspective of neuroprotection and neurogenesis. Materials and methods Kunming mice (28 ± 2 g) were randomly allocated into seven groups: control, sham, model, donepezil and SZJN groups (low, middle and high). The AD mouse model was established by A β 42 combined with scopolamine . SZJN were intragastrically administrated at doses of 0.3, 1.5 and 7.5 g/kg for 28 days. Morris water maze (MWM) test was applied to determine the cognitive function. Hematoxylin eosin (HE) and Nissl staining were carried out to evaluate pathological damages in the cortex and hippocampal tissues. To explore the protective effects of SZJN on multiple pathogenic factors of AD, protein levels of A β 42, glial fibrillary acidic protein (GFAP), Bax, Bcl-2, Caspase-3, synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), and neurogenesis related proteins were assessed using Immunofluorescence (IF) and western blot analysis . In vitro , the AD cell model was established by transduction of APP 695swe genes into Neural stem cells (NSCs) isolated from the hippocampal tissues of neonatal C57BL/6 mice. Cell viability assay and neurosphere formation assay were carried out to verify the efficacy of SZJN on proliferation of NSCs. Results Our results demonstrated that SZJN (1.5 g/kg and 7.5 g/kg) treatment significantly ameliorated cognitive deficits of AD-like mice. SZJN (7.5 g/kg) treatment significantly retarded the pathological damages including neuronal degeneration , neuronal apoptosis , Aβ peptides aggregation and reaction of astrocytes in AD-like mice. In addition, SZJN (7.5 g/kg) increased the expression of BDNF and SYP, and restored the abnormal level of MDA and SOD in the brain of AD-like mice. Furthermore, SZJN treatment for 28 days remarkably increased the proliferation of NSCs evidenced by more Nestin + and BrdU + cells in the hippocampal DG regions, and increased the amount of mature neurons marked by NeuN both in the cortex and hippocampal DG regions. In vitro , SZJN treatement (16, 32, 64 mg/ml) promoted the proliferation of NSCs evidenced by the increased amount and enlarged size of the neurospheres (p < 0.05). Conclusions Our findings indicated that SZJN could ameliorate cognitive deficits by protecting neurons from death and triggering endogenous neurogenesis. Therefore, SZJN may be considered as a promising agent to restore neuronal loss and deter the deterioration in AD patients.
研究领域:
药理学
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神经科学
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传统中药
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神经退行性疾病
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PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Yuxin Zheng,Limin Ma,Yu Wang,Jianshe Huang,Jianshan Ye,Xiurong Yang
Several different receptor candidates have been identified that bind monomeric, oligomeric, or fibrillar forms of amyloid-β (Aβ) protein, thus being involved in the clearance or cytotoxic action of Aβ. Component protein C1q, the initiator of the classical complement pathway, has been extensively reported to mediate neuroprotection or synapse loss through interactions with different effectors. Therefore, quantification of the C1q–Aβ interaction is a prerequisite for a better understanding of its implications in disease. Herein, we established a layer-by-layer interface sensing platform to precisely quantify the biomolecular interactions occurring between component C1q and amyloid-β protein 42 (Aβ42) in distinct morphological states. By leveraging the dual polarization interferometry (DPI) technique, we obtained real-time data pertaining to the mass, thickness, and density of the biomolecular layers during the binding process and calculated the binding dynamic parameters. From the in-depth analysis of the kinetic results and electrochemical verification, we determined that Aβ42 monomer (Aβ42M) exhibited a higher affinity for C1q than the Aβ42 oligomer (Aβ42O). This affinity could potentially account for the possibility that the C1q–Aβ42M interaction may be the first step to mediate the pivotal roles of C1q in Alzheimer’s disease (AD). This study provides a new perspective on the interaction between C1q and Aβ42, and it offers new information on the C1q-involved signaling pathway to advance our understanding of the molecular mechanism of AD.
研究领域:
生物化学
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分子生物学
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神经科学
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免疫学
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生物物理学
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PubMed
高影响因子
NEUROPHARMACOLOGY
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2024
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IF 4.6
He Li,Changxin Zheng,Yanru Zheng,Kai Wen,Yingjiu Zhang
Aggregation and deposition of amyloid beta-protein 1–42 (Aβ42) in the brain, primarily owing to hydrophobic interactions between Aβ42 chains, is a common pathology in all forms of Alzheimer's disease (AD). Hydrophilic oligosaccharides are widely present in the extracellular matrix and on the cytoplasmic membrane. To determine if oligosaccharides bind to Aβ42 or its aggregates and consequently affect their aggregation and cellular function, this study examined the interaction of typical functional oligosaccharides with Aβ42 or its aggregates. Isomaltooligosaccharides (IMOs), particularly isomaltotriose, panose, and isomaltotetraose, functioned as molecular chaperones for Aβ42 by binding directly to Aβ42, preserving Aβ42’s active conformation and cytotrophic activity. Oral IMOs reduced total plasma Aβ level and indirectly caused a slight reduction in the load of Aβ42 spots/plaques in the brain of AD model mice (male). Another branched oligosaccharide, bianntennary core pentasaccharide (BCP), had a relatively high binding specificity for Aβ42 oligomers (Aβ42O) and acted as an antagonistic binding partner for Aβ42O. Free BCP effectively blocked/prevented further assembly of Aβ42O and their toxicity to neural and vascular endothelial cell lines. Since BCP is also a signaling component of membrane targets (glycolipids, glycoproteins or receptors), it seemed that BCP had two opposing effects on the binding of Aβ42O to target cells. This study’s findings suggest that these branched oligosaccharides may be potential candidates for blocking or preventing Aβ42 aggregation and Aβ42O cytotoxicity/neurotoxicity, respectively, and that IMO-like or free BCP-like oligosaccharide deficiencies in the brain may be one of the underlying mechanisms for Aβ42 aggregation and Aβ42O cytotoxicity.
研究领域:
神经科学
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生物化学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Peiyao An,Mengxiao Li,Shanshan Zhang,Di Lian,Chuqi Li,Chuan Wang,Miao Yu,Duo Wang,Lingyi Kong,Jun Ren,Yue Li,Haiyan Wang,Xin Yang,Zhenlin Wu
LC sensing platform based on WGM laser is developed for the AD-related biomarker Aβ42 detection. • The sensor sensitivity is approximately 0.003 nm/pg/mL, and the LOD is 3 pg/mL. • RNA aptamer is used as recognition probes to enhance the specificity of the biosensing platform. • The combination of RNA aptamer and Aβ42 causes RI changes, resulting in WGM spectral shifts. • The structure design provides an ideal sensing platform for detecting biomedical samples. Alzheimer's disease (AD) is an irreversible and progressively worsening neurodegenerative disorder. Amyloid beta (Aβ42) plays a crucial role in the early diagnosis of this disease. However, the concentration of Aβ42 in the blood is extremely low, which poses a challenge for Aβ42 detection. Herein, a liquid crystal (LC) biosensing platform based on whispering gallery mode (WGM) laser was developed for rapid and real-time monitoring of the AD-related biomarker Aβ42. The LC microcavities were functionally modified using cetyltrimethyl ammonium bromide (CTAB) and RNA aptamers. Based on this, the quantitative monitoring mechanism of Aβ42 was analyzed, stemming from the interaction between the negatively charged RNA aptamer and CTAB, leading to the reorientation of LC molecules. This alters the refractive index distribution within the microcavity, thereby enabling the shift of the WGM spectrum. The dynamic changes of molecular orientation in the LC microcavity were monitored by polarization optical microscopy and spectral analysis. The experimental results showed that the total shifts in the resonance spectrum were directly proportional to the concentration of Aβ42 within the range of 0–1000 pg/mL. The sensitivity of the sensor is 0.003 nm/pg/mL. The experiment further confirmed the practicability of this sensor in the mouse serum. The sensor is inexpensive, easy to manufacture and fast and it is potentially useful for AD-related biomarker screening after further validation.
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
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IF 4.8
Chenchen Wang,Xiaolei Song,Diantao Chen,Junyu Su,Yong Wang,Cheng Huang,Wei Wei
Considering the irreversible nature of Alzheimer's disease (AD), early diagnosis is of great importance for AD treatment. Both β-amyloid (Aβ) and monoamine oxidase B (MAO-B) are potential biomarkers for AD. This study developed a surface-enhanced Raman scattering (SERS) sensor using gold-nanocube (OX-AuNCs) to detect Aβ42 and MAO-B. OX-AuNCs, a type of gold-nanocube with open gaps, achieved a Raman enhancement factor of 8.99 × 10 8 due to numerous hot spots. The specific affinity between Thioflavin T (ThT) and Aβ42 inhibits ThT's intramolecular rotation, reducing its SERS signal. This reduced signal showed a linear correlation with Aβ42 concentrations from 66.70 pM to 0.20 μM, achieving a limit of detection (LOD) at 44.30 pM, while also distinguishing different aggregation levels of Aβ42. Interestingly, SERS intensity of phenethylamine (PEA) also decreased significantly when interacting with MAO-B. A linear relationship was found between the change in PEA intensity and MAO-B concentration (0.01–20.00 μg mL −1 ), yielding an LOD of 5.00 ng mL −1 . The proposed SERS sensor effectively detected two potential AD biomarkers, Aβ42 and MAO-B, in artificial cerebrospinal fluid (ACSF) and human serum with satisfactory recovery rates, respectively. These results show promise for clinical diagnosis and drug screening for AD.
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PubMed
高影响因子
TALANTA
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2026
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IF 6.7
Xiangji Kong,Haoran Jiang,Biao Hu,Qiuxia Shu,Xinwei Luo,Feng Pan,Jun Hu,Zhe Wang
Amyloid-beta 42 (Aβ42) is a core biomarker associated with Alzheimer's disease (AD), but accurate quantification of low-abundance plasma Aβ42 remains challenging because of matrix interference, limited assay sensitivity, and time-consuming procedures in conventional methods. Herein, we developed an enzyme-free fluorescence biosensing platform integrating a triple-helix aptamer probe (THAP) with clamped hybridization chain reaction (cHCR), termed T-cHCR, for sensitive Aβ42 analysis. In this system, Aβ42 recognition induces controlled release of a trigger probe from the triplex-locked THAP module, which subsequently initiates a two-hairpin cHCR cascade for low-background signal amplification. Under optimized conditions, the T-cHCR assay exhibited a linear response to Aβ42 from 1 to 1000 pg/mL with a limit of detection of 1.16 pg/mL, showing an 8.1-fold lower LOD than the manufacturer-reported minimum detectable dose of the ELISA kit used in this study. The assay also displayed acceptable specificity, reproducibility, and storage stability. Preliminary analysis of clinical plasma samples showed significantly different Aβ42 levels between AD patients and age-matched healthy controls, supporting the potential of T-cHCR for further validation in plasma AD biomarker analysis. Overall, this integrated THAP-cHCR strategy provides a rapid, enzyme-free, and low-background approach for ultrasensitive plasma Aβ42 detection.
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高影响因子
Marine Drugs
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2020
·Vol. 18
·期 10
·488
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IF 4.073
Limeng Zhu,Ruilian Li,Siming Jiao,Jinhua Wei,Yalu Yan,Zhuo A. Wang,Jianjun Li,Yuguang Du
It is proven that β-amyloid (Aβ) aggregates containing cross-β-sheet structures led to oxidative stress, neuroinflammation, and neuronal loss via multiple pathways. Therefore, reduction of Aβ neurotoxicity via inhibiting aggregation of Aβ or dissociating toxic Aβ aggregates into nontoxic forms might be effective therapeutic methods for Alzheimer’s disease (AD) treatment. This study was designed to explore interference of chitosan oligosaccharides (COS) on β-(1-42)-amyloid protein (Aβ42) aggregation and Aβ42-induced cytotoxicity. Here it was demonstrated that COS showed good blood-brain barrier (BBB) penetration ability in vitro and in vivo. The experimental results showed that COS efficiently interfered with Aβ42 aggregation in dose- and degree of polymerization (DP)-dependent manners, and COS monomer with DP6 showed the best effect on preventing conformational transition into β-sheet-rich structures. Based on the binding affinity analysis by microscale thermophoresis (MST), it was confirmed that COS could directly bind with Aβ42 in a DP-dependent manner. Our findings demonstrated that different performance of COS monomers with different DPs against Aβ42 assembly was, to some extent, attributable to their different binding capacities with Aβ42. As a result, COS significantly ameliorated Aβ42-induced cytotoxicity. Taken together, our studies would point towards a potential role of COS in treatment of AD.Keywords:Alzheimer’s disease;chitosan oligosaccharides;blood-brain barrier;Aβ42;aggregation;binding affinity;cytotoxicity
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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PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2023
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IF 7.4
Jiahao Li,Wei Ni,Dan Jin,Yi Yu,Meng-Meng Xiao,Zhi-Yong Zhang,Guo-Jun Zhang
Blood-based tests have sparked tremendous attention in non-invasive early diagnosis of Alzheimer’s disease (AD), a most prevalent neurodegenerative malady worldwide. Despite significant progress in the methodologies for detecting AD core biomarkers such as Aβ42 from serum/plasma, there remains cautious optimism going forward due to its controversial diagnostic value and disease relevance. Here, a graphene electrolyte-gated transistor biosensor is reported for the detection of serum neuron-derived exosomal Aβ42 (NDE-Aβ42), which is an emerging, compelling trove of blood biomarker for AD. Assisted by the antifouling strategy with the dual-blocking process, the noise against complex biological background was considerably reduced, forging an impressive sensitivity gain with a limit of detection of 447 ag/mL. An accurate detection of SH-SY5Y-derived exosomal Aβ42 was also achieved with highly conformable enzyme-linked immunosorbent assay results. Importantly, the clinical analysis for 27 subjects revealed the immense diagnostic value of NDE-Aβ42, which can outclass that of serum Aβ42. The developed electronic assay demonstrates, for the first time, nanosensor-driven NDE-Aβ42 detection, which enables a reliable discrimination of AD patients from non-AD individuals and even the differential diagnosis between AD and vascular dementia patients, with an accuracy of 100% and a Youden index of 1. This NDE-Aβ42 biosensor defines a robust approach for blood-based confident AD ascertain.
研究领域:
神经科学
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生物传感
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生物医学工程
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诊断学
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纳米技术
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DOI
PubMed
高影响因子
Aggregate
·
2024
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IF 13.9
Manyu Zhu,Shanshan Li,Qixin Liu,Yuqi Zhang,Zihao Li,Yiran Wang,Lie Wu,Xiue Jiang
Surface chirality plays an important role in determining the biological effect, but the molecular nature beyond stereoselectivity is still unknown. Herein, through surface-enhanced infrared absorption spectroscopy, electrochemistry, and theoretical simulations, we found diasteromeric monolayers induced by assembled density on chiral gold nanofilm and identified the positive contribution of water dipole potential at chiral interface and their different interfacial interactions, which result in a difference both in the positive dipoles of interfacial water compensating the negative surface potential of the SAM and in the hindrance effect of interface dehydration, thereby regulating the interaction between amyloid-β peptide (Aβ) and N -isobutyryl-cysteine (NIBC). Water on L-NIBC interface which shows stronger positive dipole potential weakens the negative surface potential, but its local weak binding to the isopropyl group facilitates hydrophobic interaction between Aβ42 and L-NIBC and resulted fiber aggregate. Conversely, electrostatic interaction between Aβ42 and D-NIBC induces spherical oligomer. These findings provide new insight into molecular nature of chirality-regulated biological effect.
研究领域:
生物物理学
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分子生物学
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材料科学
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高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Jie Zhou,Yiwen Sun,Jin Zhang,Fusui Luo,Huili Ma,Min Guan,Junfen Feng,Xiaomeng Dong
Finding a timely, sensitive, and noninvasive detection method has become an urgent need for asymptomatic early diagnosis of Alzheimer’s disease (AD). MicroRNA-193b (miR-193b) and Aβ42 oligomers (AβO42) in neurogenic exosomes were confirmed to reflect pathological changes in the AD early stage. The combination of two biomarkers is promising for the earlier detection of AD. In this study, a detection system based on the principle of the entropy-driven strand displacement reaction (ESDR) was developed, including a dumbbell detection probe (H), an indicator probe (R), and graphene oxide (GO). In the detection system, the two hairpins of H were opened by the interaction of miR-193b (T1) and AβO42 (T2) with the aptamer. Then R hybridized with H and began to displace T, initiating the next round of ESDR to achieve sensitive detection of T. GO specifically adsorbed free R and quenched the fluorescence, further reducing the intensity of the background signal. Both of these points provided the system with a more sensitive analytical performance. The detection limit of miR-193b was 77 pM and the detection limit of AβO42 was 53 pM. This sensor detected the change of “one increase (AβO42) and one decrease (miR-193b)” in the exosome sample. Additionally, results showed that this detection system could distinguish the model of early AD from the non-AD control, which was sufficient for earlier and more sensitive detection of AD. This strategy has strong specificity, high sensitivity, and easy operation, which provides broad prospects for the early diagnosis of AD.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2025
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IF 6.1
Junli Zhang,Yanyan Zhao,Xiaochen Li,Mengchao Gu,Lijuan Xu,Jinan Zhao,Hongling Zhang
The rapid separation and detection of neuronal-derived small extracellular vesicles (EVs) in plasma is essential for diagnosing and monitoring the progression of Alzheimer's disease (AD). In this study, we present a magnetic separation-assisted visual analysis strategy for detecting Aβ42-positive EVs (Aβ42 + EVs) using a nanozyme-catalyzed colorimetric sensor. EVs are first captured from plasma using Fe 3 O 4 @SiO 2 core-shell nanoparticles functionalized with CD63 aptamers (Fe 3 O 4 @SiO 2 -Apt CD63 ). Au@Pt nanozymes, modified with Aβ42 aptamers (Au@Pt-Apt Aβ42 ), then bind to the Aβ42 protein on the EVs, forming a sandwich structure (Fe 3 O 4 @SiO 2 -EVs-Au@Pt NPs). This structure catalyzes the oxidation of the substrate 3,3′,5,5′-Tetramethylbenzidine (TMB), generating visual signals. The sensor demonstrates high sensitivity, with a detection range of 1 × 10 5 to 1 × 10 9 particles/mL and a low detection limit of 7.2 × 10 4 particles/mL. It was successfully used to detect Aβ42 + EVs in plasma samples from AD patients, showing significant promise for early AD diagnostics in clinical settings.
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高影响因子
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