JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Xiaoli Gou,Yongchun Fu,Juan Li,Juan Xiang,Minghui Yang,Yi Zhang
Nanoplastics , widely existing in the environment and organisms, have been proven to cross the blood-brain barrier, increasing the incidence of neurodegenerative diseases like Alzheimer’s disease (AD). However, current studies mainly focus on the neurotoxicity of nanoplastics themselves, neglecting their synergistic effects with other biomolecules and the resulting neurotoxicity. Amyloid β peptide (Aβ), which triggers neurotoxicity through its self-aggregation, is the paramount pathogenic protein in AD. Here, employing polystyrene nanoparticles (PS) as a model for nanoplastics, we reveal that 100 pM PS nanoparticles significantly accelerate the nucleation rate of two Aβ subtypes (Aβ 40 and Aβ 42 ) at low concentrations, promoting the formation of more Aβ oligomers and leading to evident neurotoxicity. The hydrophobic surface of PS facilitates the interaction of hydrophobic fragments between Aβ monomers , responsible for the augmented neurotoxicity. This work provides consequential insights into the modulatory impact of low-dose PS on Aβ aggregation and the ensuing neurotoxicity, presenting a valuable foundation for future research on the intricate interplay between environmental toxins and brain diseases.
研究领域:
神经科学
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环境科学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF TOXICOLOGY
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2025
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IF 1
Yanhong Fu,Jiafa Zhang,Canhong Yang,Yuanyuan Wang,Yunzhu Yang,Pingming Qiu,Weibing Xie,Shufen Zhang,Tianming Lǚ
Dimethyl sulfoxide (DMSO) is commonly used as a solvent for preparing amyloid-beta (Aβ) peptides implicated in Alzheimer’s disease. While considered relatively non-toxic at low concentrations, DMSO itself may exert biological effects that could confound experimental outcomes, especially for weakly cytotoxic substances like Aβ. Seven brain cell types (BV-2, N2a, SH-SY5Y, U87, neurons, astrocytes, microglia) were treated with varying DMSO concentrations or Aβ1-42 oligomers/protofibrils/fibrils prepared using DMSO. Cell viability was assessed by CCK-8 and LDH assays. Matched DMSO controls were prepared alongside Aβ treatments to delineate solvent effects. Low DMSO concentrations (0.0625-0.015625%) exhibited hormetic cytoprotective and growth-promoting effects, while higher concentrations (≥2%) were cytotoxic. Importantly, these hormetic solvent effects confounded the measurement of Aβ cytotoxicity. By accounting for matched DMSO controls, the study revealed that Aβ fibril toxicity may have been underestimated due to the cytoprotective solvent effects of low DMSO concentrations used in their preparation. In conclusion, DMSO exhibits complex hormetic dose-responses that can significantly influence experimental outcomes, especially for weakly cytotoxic agents like Aβ. Rigorous solvent controls are crucial to delineate genuine substance effects from potential solvent confounds and avoid erroneous interpretations.
研究领域:
神经科学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
LANGMUIR
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2024
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IF 3.7
Shenna Chen,Ronghui Li,Yanxu Liu,Ziyan Zhang,Mei Fang,Sihang Huang,Yayong Li,Lina Geng
Multifunctional nitrogen-doped carbon dots (N-CDs) were synthesized, and the morphology, composition, and spectral properties of N-CDs were characterized by multiple characterization techniques. The inhibition of β-amyloid (Aβ) peptide aggregation and the destruction of the Aβ fibril structure by N-CDs were also studied. The conformational transition and morphology of Aβ42 in the presence of N-CDs were monitored by far-UV circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The results demonstrated that the prepared N-CDs could effectively inhibit Aβ42 peptide aggregation and depolymerize Aβ fibrils. Furthermore, the inhibition and disaggregation mechanism of existing Aβ42 fibrils by N-CDs was studied by electron paramagnetic resonance spectroscopy (EPR). The results showed that the modulation of reactive oxygen species (ROS) by N-CDs and multiple interactions between N-CDs and Aβ42 fibrils played a crucial part in restraining and reducing the aggregation of Aβ42. Our work demonstrates the therapeutic potential of N-CDs in suppressing Aβ42 peptide aggregation and destroying existing Aβ42 fibrils, which provides a new perspective strategy in the treatment of Alzheimer’s disease (AD).
研究领域:
生物化学
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医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2024
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IF 3.8
Wei Yuxin,Bai Qingqing,Ning Xinlu,Bai Xiaofan,Lv Jie,Li Meng
Sensitive and accurate detection of the amyloid-β (Aβ) monomer is of fundamental significance for early diagnosis of Alzheimer’s disease (AD). Herein, inspired by the specific Cu-Aβ monomer coordination, a cutting-edge colorimetric assay based on single-atom Cu anchored N-doped carbon nanospheres (Cu-NCNSs) was developed for Aβ monomer detection and an amyloidogenesis study. By directly pyrolyzing Cu 2+ -incorporated covalent organic frameworks (COFs), the resulting Cu-NCNSs with a high loading of Cu (8.04 wt %) exhibited outstanding peroxidase-like activity. The strong binding affinity of Aβ monomer to Cu-NCNSs effectively inhibited their catalytic activity, providing the basis for the colorimetric assay. The Cu-NCNSs-based sensor showed a detection limit of 1.182 nM for Aβ monomer, surpassing traditional techniques in terms of efficiency, accuracy and simplicity. Moreover, the system was successfully utilized for Aβ monomer detection in rat cerebrospinal fluid (CSF). Notably, the distinct inhibitory effects of monomeric and aggregated Aβ species on the catalytic activity of Cu-NCNSs were allowed for monitoring of the dynamic aggregation process of Aβ. Compared to thioflavin T (ThT), the most widely used amyloid dye, the detection system exhibited greater sensitivity towards toxic Aβ oligomers, which was crucial for early AD diagnosis and treatment. Our work not only sheds light on the rational design of highly active single-atom nanozymes from COFs but also expands the potential applications of nanozymes in early disease diagnosis. Graphical
研究领域:
生物化学
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医学诊断
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纳米材料科学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Qiwen Peng,Min Zhang,Guoyue Shi
An amyloid-beta peptide (Aβ) is generally believed to be a pathological marker of Alzheimer’s disease (AD), but it is still of great significance to explore the upstream and downstream relationship of Aβ in AD. It is previously reported that c-Abl, a nonreceptor tyrosine kinase, can be activated by Aβ, but the interaction between Aβ and c-Abl is still unknown. Herein, an extended-gate field-effect transistor (EG-FET)-based sensor has been developed to monitor the level of c-Abl with high sensitivity and selectivity. Our peptide-functionalized EG-FET sensor as the signal transducer can follow c-Abl activity with electron transfer by its specific phosphorylation. The sensor presents a good linear correlation over c-Abl concentrations of 1 pg/mL to 3.05 μg/mL. The sensor was successfully applied to quantify c-Abl activity in the brain tissue of AD transgenic mice, and the interaction between c-Abl and Aβ in AD mice was explored by administering the c-Abl inhibitor (imatinib) and the agonist (DPH). Our work is expected to provide an important reference for early diagnosis and treatment of AD.
研究领域:
生物医学工程
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Xiaolei Song,Chenchen Wang,Qin Ding,Peng Li,Shihao Sun,Wei Wei,Juan Zhang,Rongli Sun,Lihong Yin,Songqin Liu,Yuepu Pu
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important pathological event that promotes AD progression. However, therapeutic strategies toward only Aβ or microglial modulation still have many problems. Herein, inspired by the Aβ transportation, an Aβ-derived peptide (CKLVFFAED) engineered biomimetic nanodelivery system (MK@PC-R NPs) is reported for realizing BBB penetration and reprogram neuron and microglia in AD lesion sites. This hollow mesoporous Prussian blue-based MK@PC-R NPs carrying curcumin and miRNA-124 can down-regulate β secretase expression, thereby inhibiting Aβ production and reducing Aβ-induced neurotoxicity. Meanwhile, MK@PC-R NPs with excellent antioxidant and anti-inflammatory properties could normalize the microglial phenotype and promote Aβ degradation, providing neuroprotection. As expected, after treatment with MK@PC-R NPs, the Aβ burdens, neuron damages, neuroinflammation, and memory deficits of transgenic AD mice (APP/PS1 mice) are significantly attenuated. Overall, this biomimetic nanodelivery system with anti-Aβ and anti-inflammatory properties provides a promising strategy for the multi-target therapy of early AD.
研究领域:
神经科学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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