Serum albumin-embedding copper nanoclusters inhibit Alzheimer's β-amyloid fibrillogenesis and neuroinflammation
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View abstract on PubMed
Summary
This summary is machine-generated.New copper nanoclusters (CuNCs@HSA) effectively scavenge reactive oxygen species (ROS), inhibit amyloid-beta (Aβ) aggregation, and reduce neuroinflammation, offering a promising treatment for Alzheimer
Area Of Science
- Nanomedicine
- Neuroscience
- Biochemistry
Background
- Alzheimer's disease (AD) pathogenesis involves reactive oxygen species (ROS), amyloid-beta (Aβ) aggregation, and neuroinflammation.
- Current AD treatments are limited, necessitating novel therapeutic strategies targeting multiple pathological hallmarks.
- Nanomaterials offer potential for multifunctional therapeutic interventions in AD.
Purpose Of The Study
- To design and synthesize human serum albumin (HSA)-embedded copper nanoclusters (CuNCs@HSA) for simultaneous ROS elimination, Aβ aggregation inhibition, and neuroinflammation mitigation.
- To evaluate the enzyme-like activities, Aβ inhibitory effects, cellular protective capabilities, and anti-neuroinflammatory properties of CuNCs@HSA.
- To assess the in vivo efficacy of CuNCs@HSA in a C. elegans model of Alzheimer's disease.
Main Methods
- Fabrication of ultrasmall copper nanoclusters (CuNCs) embedded within human serum albumin (HSA) using an HSA-mediated strategy.
- Characterization of CuNCs@HSA's enzyme-like activities (superoxide dismutase, catalase, glutathione peroxidase, hydroxyl radical scavenging).
- In vitro assays assessing Aβ fibrillization inhibition, protection against Aβ-induced cellular damage and oxidative stress, and mitigation of neuroinflammation in BV-2 cells.
- In vivo studies in transgenic C. elegans to evaluate plaque formation, ROS levels, and lifespan extension.
Main Results
- CuNCs@HSA demonstrated potent superoxide dismutase (>5000 U/mg), catalase, glutathione peroxidase activities, and hydroxyl radical scavenging.
- CuNCs@HSA significantly inhibited Aβ fibrillization (2.5-fold higher potency than HSA) and protected cells from Aβ-induced toxicity and oxidative stress.
- CuNCs@HSA alleviated neuroinflammatory cytokine secretion (TNF-α, IL-6) in lipopolysaccharide-stimulated BV-2 cells.
- In vivo, CuNCs@HSA suppressed plaque formation, reduced ROS levels, and extended the lifespan of transgenic C. elegans by 5 days.
Conclusions
- HSA-templated CuNCs represent a promising nanotherapeutic agent for Alzheimer's disease.
- CuNCs@HSA effectively targets multiple AD pathologies, including ROS accumulation, Aβ aggregation, and neuroinflammation.
- The developed nanomaterial shows significant therapeutic potential for Alzheimer's disease treatment, supported by both in vitro and in vivo evidence.
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