1. A Ru 3+ -functionalized-NMOF nanozyme as an inhibitor and disaggregator of β-amyloid aggregates.
- Author
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Luo WC, Bao LN, Zhang Y, Zhang ZT, Li X, Pan MM, Zhang JT, Huang K, Xu Y, and Xu L
- Subjects
- Animals, Metal-Organic Frameworks chemistry, Metal-Organic Frameworks pharmacology, Caenorhabditis elegans metabolism, Caenorhabditis elegans drug effects, Humans, Particle Size, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Reactive Oxygen Species metabolism, Amyloid beta-Peptides antagonists & inhibitors, Amyloid beta-Peptides metabolism, Protein Aggregates drug effects, Ruthenium chemistry, Ruthenium pharmacology
- Abstract
Alzheimer's disease (AD) heavily impacts human lives and is becoming serious as societies age. Inhibiting and disaggregating β-amyloid aggregates is a possible solution for AD therapy. In this study, a novel type of nanozyme based on Ru
3+ -chelated nanoscale metal organic frameworks (Ru3+ -NMOFs), displaying strong peroxidase-like activity, was proposed as an inhibitor and disaggregator of β-amyloid aggregates. As a high concentration of hydrogen peroxide is present at the sites of β-amyloid aggregates, Ru3+ -NMOFs could catalyze the conversion of hydrogen peroxide to hydroxyl radicals. Thus, these hydroxyl radicals would attack the β-amyloid chain, oxidizing it to enhance its hydrophilicity, which results in a decreased hydrophobic interaction and reduced degree of aggregation. Ru3+ -NMOFs could effectively inhibit as well as disaggregate β-amyloid fibrils both in vitro and in vivo . Additionally, the reduction of the β-amyloid aggregates and the attenuation of reactive oxygen species transfer led to lower levels of inflammatory factors, which could be beneficial in alleviating AD symptoms. In a typical treatment, Ru3+ -NMOFs could mitigate the paralysis of C. elegans CL2120 and elevate survival rates. This study opens a new avenue for MOF-based nanozymes as potential treatment agents for AD therapy.- Published
- 2024
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