Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential
To slow the progression of Alzheimer’s disease (AD), eliminating amyloid β (Aβ) or inhibiting its abnormal aggregation has emerged as a promising strategy. Among the molecules developed to inhibit Aβ aggregation, gold nanoclusters (AuNCs) stand out due to their excellent biocompatibility and high ef...
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Elsevier
2025-06-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127525004526 |
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| author | Ye-Cheng Wang Si-Cong Bai Xue-Ying Hu Jia-Yi Lin Wei-Lin Ye Huan-Zhang Xie Liu Hong Gao Li |
| author_facet | Ye-Cheng Wang Si-Cong Bai Xue-Ying Hu Jia-Yi Lin Wei-Lin Ye Huan-Zhang Xie Liu Hong Gao Li |
| author_sort | Ye-Cheng Wang |
| collection | DOAJ |
| description | To slow the progression of Alzheimer’s disease (AD), eliminating amyloid β (Aβ) or inhibiting its abnormal aggregation has emerged as a promising strategy. Among the molecules developed to inhibit Aβ aggregation, gold nanoclusters (AuNCs) stand out due to their excellent biocompatibility and high efficiency in modulating Aβ aggregation. However, the currently reported AuNCs often lack specificity toward Aβ, which may limit their in vivo applications. In this study, we synthesized a novel gold nanocluster (AuCRHA1) functionalized with the peptide CRHRHKLVFF to achieve specific recognition of Aβ. Our results demonstrated that AuCRHA1 effectively inhibited Aβ aggregation and reduced its cytotoxicity in complex solutions, underscoring the robustness of our design. By combining isothermal titration calorimetry results with mathematical modeling, molecular docking, and molecular dynamics simulation, we identified two main inhibitory roles of AuCRHA1: binding to free Aβ monomers to reduce the effective Aβ concentration and depolymerizing mature fibrils. Moreover, treatment with AuCRHA1 significantly extended the lifespan of Caenorhabditis elegans, an AD model organism. Collectively, this work highlights the potential of AuCRHA1 as a promising agent for inhibiting Aβ aggregation and its application in preventing or treating AD. |
| format | Article |
| id | doaj-art-5ae1d37745bf4f8ea2ab086a19b6dde9 |
| institution | OA Journals |
| issn | 0264-1275 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-5ae1d37745bf4f8ea2ab086a19b6dde92025-08-20T02:35:36ZengElsevierMaterials & Design0264-12752025-06-0125411403210.1016/j.matdes.2025.114032Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potentialYe-Cheng Wang0Si-Cong Bai1Xue-Ying Hu2Jia-Yi Lin3Wei-Lin Ye4Huan-Zhang Xie5Liu Hong6Gao Li7Fuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, China; College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350108, ChinaSchool of Future Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, ChinaFuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, ChinaFuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, ChinaFuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, China; College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350108, ChinaFuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, China; Corresponding authors.School of Mathematics, Sun Yat-sen University, Guangzhou 510275, China; Corresponding authors.Fuzhou Institute of Oceanography, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, China; Corresponding authors.To slow the progression of Alzheimer’s disease (AD), eliminating amyloid β (Aβ) or inhibiting its abnormal aggregation has emerged as a promising strategy. Among the molecules developed to inhibit Aβ aggregation, gold nanoclusters (AuNCs) stand out due to their excellent biocompatibility and high efficiency in modulating Aβ aggregation. However, the currently reported AuNCs often lack specificity toward Aβ, which may limit their in vivo applications. In this study, we synthesized a novel gold nanocluster (AuCRHA1) functionalized with the peptide CRHRHKLVFF to achieve specific recognition of Aβ. Our results demonstrated that AuCRHA1 effectively inhibited Aβ aggregation and reduced its cytotoxicity in complex solutions, underscoring the robustness of our design. By combining isothermal titration calorimetry results with mathematical modeling, molecular docking, and molecular dynamics simulation, we identified two main inhibitory roles of AuCRHA1: binding to free Aβ monomers to reduce the effective Aβ concentration and depolymerizing mature fibrils. Moreover, treatment with AuCRHA1 significantly extended the lifespan of Caenorhabditis elegans, an AD model organism. Collectively, this work highlights the potential of AuCRHA1 as a promising agent for inhibiting Aβ aggregation and its application in preventing or treating AD.http://www.sciencedirect.com/science/article/pii/S0264127525004526Amyloid βGold nanoclusterPeptideInhibitorAlzheimer’s disease |
| spellingShingle | Ye-Cheng Wang Si-Cong Bai Xue-Ying Hu Jia-Yi Lin Wei-Lin Ye Huan-Zhang Xie Liu Hong Gao Li Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential Materials & Design Amyloid β Gold nanocluster Peptide Inhibitor Alzheimer’s disease |
| title | Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential |
| title_full | Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential |
| title_fullStr | Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential |
| title_full_unstemmed | Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential |
| title_short | Aβ aggregation inhibition via peptide-conjugated gold nanoclusters: Mechanistic insights and therapeutic potential |
| title_sort | aβ aggregation inhibition via peptide conjugated gold nanoclusters mechanistic insights and therapeutic potential |
| topic | Amyloid β Gold nanocluster Peptide Inhibitor Alzheimer’s disease |
| url | http://www.sciencedirect.com/science/article/pii/S0264127525004526 |
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