INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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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
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
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2025
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IF 4.2
Pengbo She,Lei Xing,Mingyang Zhou,Shu Xing,Yaozheng Yang,Xiuxiu Li,Xuanxuan Ma,Tao Cheng,Jinjian Wei,John K. Bielicki,Jing Xu
The utilization of near-infrared fluorescent probes for the detection of amyloid-β (Aβ) in Alzheimer's disease (AD) has been extensively investigated. Nevertheless, the development of probes that can simultaneously meet the requirements for rapid, accurate, and visual detection remains challenging. In this study, a novel Aβ-targeted fluorescent probe, designated NQM-FN , has been designed based on a D-π-A structural framework. NQM-FN incorporates quinoline-malononitrile (QM) as the fluorescent component and N,N- dimethylmino as the recognition unit. By utilizing a push-pull electronic conjugation system (with N,N- dimethylmino as electron donor; sulfonic acid and cyanide groups as electron acceptors), NQM-FN induces near-infrared emission and enhances blood-brain barrier (BBB) permeability. Fluorescence analysis indicated that NQM-FN is non-emissive in aqueous environments due to aggregation-caused quenching (ACQ), yet it demonstrates robust fluorescence in organic solvents, such as ethanol. When bound to Aβ aggregates, conformational rigidification suppresses twisted intramolecular charge transfer (TICT), facilitating rapid ‘off-on’ detection with increased emission intensity. NQM-FN interacts with Aβ42 aggregates in PBS solution, showing a rapid “off-on” switch (approximately 10 s). MTT assays revealed that the NQM-FN probe has good cellular compatibility, sustaining over 80 % cell viability. Confocal laser scanning microscopy (CLSM) imaging confirmed the successful real-time, sensitive, and visual detection of Aβ42 aggregates within live cells using the NQM-FN probe. This research introduces an innovative method for synthesizing fluorescent probes for the detection of Aβ42 aggregates, and the developed NQM-FN probe shows great promise as a tool for fluorescent detection.
研究领域:
生物化学
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医学诊断
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分子探针设计
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DOI
高影响因子
BIOORGANIC CHEMISTRY
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2022
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IF 5.307
Yuanyuan Liu,Chu Han,Rongji Dai,Bo Li
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the extracellular amyloid plaques in the brain. Recent studies have shown that ferroptosis , a recently identified cell death pathway associated with the accumulation of lipid hydroperoxides, is closely related to the occurrence and exacerbation of AD. The application of ferroptosis inhibitors can alleviate the development of AD in both cellular and animal models. Herein, a series of dual-functional hydroxylated chalcone derivatives by integrating the heterocyclic dimethylaminopyrimidine in the core structure were designed and synthesized beyond our previous research to optimize their inhibition activities towards Aβ protein aggregation and ferroptosis simultaneously. The inhibitory ability of the novel synthesized chalcone derivatives were greatly improved. The results indicated that the introduction of the dimethylaminopyrimidine structure provided improved effect on Aβ protein aggregation inhibitory activity in both solution and cellular models. Trihydroxy chalcone derivative A-N-5 provided the best inhibition activities against Aβ protein aggregation in cellular models. The trihydroxy compound A-N-5 did not show cytotoxicity at the concentration lower than 100 µM (with IC 50 > 1 mM), but had a significant effect on promoting cell proliferation. Results indicated that compound A-N-5 could potentially promote neuronal cell growth in the damaged brain tissue. The compound could also inhibit ferroptosis induced by RSL or erastin and reduce the lipid peroxidation levels induced by Aβ 1-42 protein aggregation. Molecular docking was also conducted to explain the better inhibitory effect of novel compounds to inhibit Aβ protein aggregation compared to the previous designed molecules without incorporation of the dimethylaminopyrimidine. In summary, the trihydroxy compound A-N-5 showed the best inhibition activities against Aβ aggregation as well as ferroptosis with low cytotoxicity as a promising molecular skeleton candidate for further development of lead compound for in vivo test to treat AD.
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
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DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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