Evidence-based Complementary and Alternative Medicine
·
2019
·
IF 1.984
Ling Zhou,Pan-Pan Huang,Lin-Lin Chen,Ping Wang
The deposition of amyloid beta (Aβ) is the main hallmark of Alzheimer’s disease (AD) and there is no effective drug to cure the progressive cognitive loss or memory deficits caused by the aggregative toxicity of Aβ protein. Oxidative stress has been hypothesized to play a role in progressive neurodegenerative diseases like AD. Panax notoginseng saponin (PNS) from the rhizome of “pseudo-ginseng” exhibits potent antioxidant effects on aging process in neuron cells and animals. By using C. elegans as an ideal model organism, the present study shows that PNS (0.5–4 mg/mL) can significantly inhibit AD-like symptoms of worm paralysis and enhance resistance to oxidative stress induced by paraquat and aging conditions. Additionally, PNS extends lifespan and maintains healthspan of C. elegans by improving the swimming prowess and fertility at old age. It markedly activates the expression of SKN-1 mRNA, which further supports SKN-1 signaling pathway which is involved in the therapeutic effect of PNS on AD C. elegans. Our results provide direct evidence on PNS for treating AD on gene level and theoretical foundation for reshaping medicinal products of PNS in the future.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Xingyuan Wang,Longjian Zhou,Yayue Liu,Fangfang Ban,Zhiyou Yang,Yongping Zhang,Xueqiong Hu,Yi Zhang
Screening Aβ aggregation inhibitors (AAIs) is important for Alzheimer's disease drug discovery. However, common cellular or biochemical methods are not suitable for high-throughput natural product screening. A gold nanoparticle (GNP) screening method was employed in this study to screen marine fungal crude extracts and pure compounds for quick AAI discovering. The anti-Aβ aggregation activity was further inspected using transmission electron microscopic (TEM) observation, and the interaction between active molecules and different Aβ species was revealed by molecular docking. The results indicated that the fungal extracts DLS2008001(M), BM3T2(M), DLEN2008005(M), TBG1-16(P), and TBG1-13(P) showed activity comparable to the positive control human serum albumin at the concentration of 500 µg/mL; 10 pure compounds also displayed moderate anti-aggregation activity, particularly nidulin, aspergillusidone G, and butyrolactone I. The inspection of anti-Aβ aggregation effect through TEM further demonstrated that extracts TBG1-16(P), DLS2008001(M), and BM3T2(M) dramatically inhibited the formation of Aβ aggregates. Molecular docking displayed low binding energies and key interactions of nidulin, aspergillusidone G, and butyrolactone I, with nine types of Aβ peptides. These findings indicate that the GNP method is efficient in screening AAIs and reveal marine fungal natural products as valuable sources of small molecular AAIs. Graphical GRAPHICAL
研究领域:
神经科学
·
药理学
·
生物技术
·
分子生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2021
·
IF 3.921
Ying Xu,Yunxia Dong,Cong Wang,Qian Jiang,Haichao Chu,Yue Tian
As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro . In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ 1-40 and Aβ 1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.
研究领域:
神经科学
·
药理学
·
麻醉学
·
老年医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Yan Zhou,Jia Liu,Tingting Zheng,Yang Tian
The aggregation of Aβ has been reported to closely correlate with Alzheimer’s disease (AD). However, clear monitoring of the entire aggregation process of Aβ from monomer to fibril has been scarcely reported until now. Herein, we developed a label-free ratiometric surface enhanced Raman spectroscopic (SERS) platform for real-time monitoring of the entire process of Aβ aggregation in neurons and brain tissues. Different gold nanoparticles, generated in situ with Aβ monomer and fibril as templates separately, were served as effective SERS substrates to achieve a high sensitivity with a limit of detection (LOD) down to 70 ± 4 pM and 3.0 ± 0.5 pM for Aβ40 monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of Aβ monomer and fibril (I1244/I1268) realized real-time monitoring of the entire aggregation process of Aβ monomer with high accuracy and selectivity against other proteins and amino acids. The significant analytical performance of the developed platform, together with good biocompatibility, long-term stability, and remarkable spatial resolution, enabled the present SERS platform imaging and real-time monitoring and imaging of Aβ aggregation influenced by different metal ions (Cu2+, Zn2+, and Fe3+) in neurons and brain tissues at the single cell level. Our results suggested that Cu2+ and Zn2+ ion of low concentration (10 μM) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 μM) showed inhibition of fibrosis.
研究领域:
生物化学
·
医学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2025
·
IF 4.2
Jun Fu,Chengjie Ding,Wenqing Li,Jiali Lei,He Wang,Lingfei Meng,Xiaoya Lin,Weiyuan Chen,Hongchang Gao
Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, with hallmark pathological features including Aβ deposition and tau protein hyperphosphorylation. These pathological alterations are particularly prominent in the Prefrontal Cortex (PFC) and exert profound effects on cognitive function. The present study aimed to reveal key proteins in the PFC and provide insight into their potential mechanisms of action in AD. Accordingly, proteomic analysis was conducted to profile differential proteins in 5 × FAD mice, followed by in vivo and in vitro validation of core proteins through AAV-mediated interference of target gene expression. Furthermore, transcriptomics and molecular biology techniques were employed to confirm the underlying mechanisms of action of core proteins in AD. The results demonstrated that ELAVL1 was significantly upregulated in the PFC of AD mice. Behavioral experiments revealed that inhibition of ELAVL1 expression markedly improved long-term memory in AD mice. Immunostaining and Western blot analyses confirmed that suppressing ELAVL1 expression alleviated Aβ1–42 deposition and apoptosis. In vitro experiments indicated that knocking down ELAVL1 significantly reduced the apoptotic response of SH-SY5Y cells induced by Aβ1–42 and APP/Swe cells. Transcriptomic analysis further revealed that ELAVL1 regulates Aβ1–42-induced apoptosis via activation of the Bcl-2/Bax pathway. Notably, immunofluorescence co-localization staining and pull-down assays confirmed that ELAVL1 directly interacts with APP. Collectively, these findings provide valuable insights into the molecular mechanisms underlying AD and suggest ELAVL1 as a promising therapeutic target for AD.
✓ 已验证
DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2018
·
IF 3.076
Hao Song,Li-Ping Huang,Yuping Li,Chao Liu,Songhua Wang,Wei Meng,Shanshan Wei,Xin-Ping Liu,Yanchun Gong,Li-Hua Yao
In Alzheimer’s disease (AD), β-amyloid (Aβ) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Aβ-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Aβ-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Aβ 25–35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Aβ 25–35 -induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis. Cordycepin inhibits ROS production, elevated levels of Ca 2+ induced by Aβ 25–35 , and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis. In addition, it decreases the increased p-Tau expression that plays a key role in the initiation of the AD. Results showed that the anti-apoptotic effects of cordycepin are partially dependent on the activation of adenosine A 1 receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders, such as AD.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Dan Tao,Chang Xie,Sinan Fu,Shuang Rong,Shizhen Song,Huarong Ye,Nicole Jaffrezic-Renault,Zhenzhong Guo
How to sensitively detect early biomarkers of Alzheimer's disease (AD) is nowadays, one of the major challenges. In this work, Aβ oligomers (AβO), one of the AD biomarkers, was analyzed using an electrochemical aptasensor , which was prepared based on thionine (Th) - functionalized three - dimensional carbon nanomaterials (reduced graphene oxide (rGO) and multi-wall carbon nanotubes (MWCNTs)) immobilized DNA-aptamer. Th, a positively charged planar aromatic molecule, form many π - π conjugated structures with rGO and MWCNTs, then improving the structural stability, electron transfer and the capacitive properties of Th-rGO-MWCNTs nanocomposites. Under the optimal conditions, differential pulse voltammetry (DPV) current responses decreased with the increase of AβO concentration. The obtained AβO aptasensor presented a wide linear range of 0.0443 pM–443.00 pM and limit of detection (LOD) was 10 fM. Meanwhile, AβO aptasensor displayed remarkable stability and selectivity . It has a great potential for early diagnosis of AD in human real serum samples.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neurotherapeutics
·
2025
·
IF 6.9
Yue Zhang,Lan Deng,Jing Wei,Lufen Huang,Fei Gao,Lu Yu,Fengdan Zhu,Jianing Mi,Jianming Wu,Fang Ren,Minsong Guo,Xiaogang Zhou,Dalian Qin,Ting Chen,Anguo Wu
Alzheimer's disease (AD) pathology involves amyloid-beta (Aβ) accumulation and neuronal toxicity, highlighting the need for therapeutic strategies that can both inhibit Aβ aggregation and promote pathogenic protein clearance. In this study, we identified Gaultheria leucocarpa as a medicinal plant with promising neuroprotective potential. Thioflavin T (ThT) fluorescence screening revealed that extracts from G. leucocarpa (GE), particularly the petroleum ether fraction of G. leucocarpa extract (GPF), effectively inhibited Aβ fibril formation in vitro . In cell-based assays, GPF significantly improved the viability of PC-12 cells exposed to Aβ peptides and fibrils, indicating protection against Aβ-induced cytotoxicity. Furthermore, GPF enhanced mitophagic activity, as demonstrated by increased GFP-LC3 puncta, elevated LC3-II/I ratio, and colocalization of GFP-LC3 with MitoTracker Red. Mechanistic investigations showed that GPF activates mitophagy via the AMPK/ULK1 pathway and inhibits the PI3K/AKT/mTOR pathway, resulting in enhanced degradation of APP and Tau proteins. In Caenorhabditis elegans models relevant to AD, GPF administration led to reduced Aβ deposits, delayed paralysis onset, improved food perception, and decreased oxidative stress. Collectively, these findings demonstrate that GPF exerts dual actions by inhibiting Aβ fibrillization and promoting mitophagy-mediated degradation of pathogenic proteins. The active ingredients identified from GPF extracts represent promising leads for the development of novel neuroprotective agents targeting AD-related pathological mechanisms.
研究领域:
神经科学
·
药理学
·
生物化学
·
细胞生物学
·
药物化学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 17
·3489
·
IF 4.6
Xiaohua Wang,Minglan Ma,Yalan Feng,Jian Liu,Gang Wang
A novel series of multifunctional tacrine–quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer’s agents. These compounds incorporate tacrine for cholinesterase’s inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation–π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds16e(IC50= 0.10 μM for AChE, 0.043 μM for BuChE) and16h(IC50= 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-induced Aβ1–42aggregation (16e: 80.5% ± 4.4%, 16h: 93.2% ± 3.9% at 20 μM). Kinetic analyses revealed mixed-type inhibition, suggesting dual binding to both CAS and PAS of AChE. UV–vis spectrometry confirmed the chelation of Cu2+and Zn2+ions by the 8-hydroxyquinoline moiety. These findings highlight the tacrine–quinoline scaffold as a promising platform for the discovery of a multitarget-directed anti-AD drug.
研究领域:
药物化学
·
神经药理学
·
生物有机化学
·
药物设计
·
阿尔茨海默病研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2020
·
IF 1.345
Min-Ye Huang,Gu-Ran Yu
This study aimed to evaluate the effect Cycloastragenol (CAG), a triterpenoid saponin isolated from the Radix astragali, on Aβ-induced BBB damage. An immortalized endothelial cell line (bEnd.3) was employed to mimic a BBB. The Western blot, TUNEL staining, Flow cytometric analysis and Enzyme-linked immunosorbent assay were performed. The present results showed that CAG (10, 50, 75 μM) can alleviate oligomer Aβ1–42 induced bEnd.3 cell apoptosis and increase tight junction scaffold proteins expression. The result also indicated that CAG increased soluble Aβ efflux across BBB via upregulation of the P-gp and downregulation of RAGE expression.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Ying Wang,Qiong Cheng,Qina Su,Xuesong Yu,Tianqi Shen,Xiaoling Yang,Weizhang Jia
Aesculin , a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis . However, the regulatory mechanisms remain poorly characterized in vivo . This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-β (Aβ)-mediated neurotoxicity in Caenorhabditis elegans . Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aβ-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aβ-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aβ-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aβ-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes .
研究领域:
分子生物学
·
神经科学
·
药理学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yadan Zhang,Xiaoyu Zhang,Jie Zhou,Yuting Li,Tianhan Kai,Lin Zhang
Alzheimer's disease (AD) is predominantly characterized by cholinergic dysfunction, mitochondrial impairment, oxidative stress, and inflammation, primarily driven by amyloid-beta (Aβ) peptides. This study investigates the protective effects of Lycium ruthenicum Murray–derived exosome-like nanoparticles (LELN) in AD models using transgenic Caenorhabditis elegans ( C. elegans ). Findings showed that C. elegans effectively internalized LELN, which remained stable in vivo. Compared with untreated controls, treatment with 600 μg/mL LELN significantly extended the lifespan of CL4176 [ myo-3p ::Aβ 1–42 ] and CL2006 [ unc-54 /Aβ 1–42 ] worms by 34.78 % and 34.85 %, respectively, and delayed Aβ-induced paralysis by 52.42 % and 42.72 %, respectively. Furthermore, LELN increased the chemotaxis index of CL2355 [ snb-1 ::Aβ 1–42 ] worms from 11.11 % to 55.56 %. Mechanistically, LELN reduced the levels of Aβ oligomers and monomers via the DAF-16 pathway, consequently alleviating AD-like symptoms in transgenic C. elegans . The effects of LELN include inhibiting acetylcholinesterase activity to mitigate cholinergic dysfunction, restoring mitochondrial membrane potential and adenosine triphosphate production to ameliorate mitochondrial dysfunction, and reducing oxidative stress and inflammation. Collectively, these results highlight the protective role of LELN against Aβ-induced AD pathology and underscore their potential as a therapeutic candidate for AD treatment.
研究领域:
神经生物学
·
分子生物学
·
药理学
✓ 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）