Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols
Abstract Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins....
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-54464-4 |
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| author | Behnaz Mirzaei-Behbahani Ali Akbar Meratan Beitollah Moosakhani Mahya Mohammad-Zaheri Zahra Mousavi-Jarrahi Nasser Nikfarjam Mohammad Bagher Shahsavani Ali Akbar Saboury |
| author_facet | Behnaz Mirzaei-Behbahani Ali Akbar Meratan Beitollah Moosakhani Mahya Mohammad-Zaheri Zahra Mousavi-Jarrahi Nasser Nikfarjam Mohammad Bagher Shahsavani Ali Akbar Saboury |
| author_sort | Behnaz Mirzaei-Behbahani |
| collection | DOAJ |
| description | Abstract Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins. However, the clinical applications of GTPs in amyloid-related diseases have been greatly limited by drawbacks such as poor chemical stability and low bioavailability. To address these limitations, this study utilized an Iranian green tea polyphenolic extract as a reducing agent to neutralize silver ions and facilitate the formation of silver nanoparticle capped by GTPs (GTPs-capped AgNPs). The results obtained from this study demonstrate that GTPs-capped AgNPs are more effective than free GTPs at inhibiting amyloid fibrillation and reducing cytotoxicity induced by amyloid fibrils of human insulin and α-synuclein (α-syn). This improved efficacy is attributed to the increased surface/volume ratio of GTPs-capped AgNPs, which can enhance their binding affinity to amyloidogenic species and boosts their antioxidant activity. The mechanism by which GTPs-capped AgNPs inhibit amyloid fibrillation appears to vary depending on the target protein. For structured protein human insulin, GTPs-capped AgNPs hinder fibrillation by constraining the protein in its native-like state. In contrast, GTPs-capped AgNPs modulate fibrillation of intrinsically disordered proteins like α-syn by redirecting the aggregation pathway towards the formation of non-toxic off-pathway oligomers or amorphous aggregates. These findings highlight polyphenol-functionalized nanoparticles as a promising strategy for targeting protein aggregates associated with neurodegenerative diseases. |
| first_indexed | 2024-03-07T14:59:37Z |
| format | Article |
| id | doaj.art-a05b0ee1006e493f962acc9511317d7c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T14:59:37Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a05b0ee1006e493f962acc9511317d7c2024-03-05T19:12:44ZengNature PortfolioScientific Reports2045-23222024-02-0114111710.1038/s41598-024-54464-4Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenolsBehnaz Mirzaei-Behbahani0Ali Akbar Meratan1Beitollah Moosakhani2Mahya Mohammad-Zaheri3Zahra Mousavi-Jarrahi4Nasser Nikfarjam5Mohammad Bagher Shahsavani6Ali Akbar Saboury7Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS)Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS)Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS)Institute of Biochemistry and Biophysics, University of TehranInstitute of Biochemistry and Biophysics, University of TehranDepartment of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS)Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz UniversityInstitute of Biochemistry and Biophysics, University of TehranAbstract Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins. However, the clinical applications of GTPs in amyloid-related diseases have been greatly limited by drawbacks such as poor chemical stability and low bioavailability. To address these limitations, this study utilized an Iranian green tea polyphenolic extract as a reducing agent to neutralize silver ions and facilitate the formation of silver nanoparticle capped by GTPs (GTPs-capped AgNPs). The results obtained from this study demonstrate that GTPs-capped AgNPs are more effective than free GTPs at inhibiting amyloid fibrillation and reducing cytotoxicity induced by amyloid fibrils of human insulin and α-synuclein (α-syn). This improved efficacy is attributed to the increased surface/volume ratio of GTPs-capped AgNPs, which can enhance their binding affinity to amyloidogenic species and boosts their antioxidant activity. The mechanism by which GTPs-capped AgNPs inhibit amyloid fibrillation appears to vary depending on the target protein. For structured protein human insulin, GTPs-capped AgNPs hinder fibrillation by constraining the protein in its native-like state. In contrast, GTPs-capped AgNPs modulate fibrillation of intrinsically disordered proteins like α-syn by redirecting the aggregation pathway towards the formation of non-toxic off-pathway oligomers or amorphous aggregates. These findings highlight polyphenol-functionalized nanoparticles as a promising strategy for targeting protein aggregates associated with neurodegenerative diseases.https://doi.org/10.1038/s41598-024-54464-4GTPsGTPs-capped AgNPsAmyloid fibrilCytotoxicityHuman insulinα-Synuclein |
| spellingShingle | Behnaz Mirzaei-Behbahani Ali Akbar Meratan Beitollah Moosakhani Mahya Mohammad-Zaheri Zahra Mousavi-Jarrahi Nasser Nikfarjam Mohammad Bagher Shahsavani Ali Akbar Saboury Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols Scientific Reports GTPs GTPs-capped AgNPs Amyloid fibril Cytotoxicity Human insulin α-Synuclein |
| title | Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| title_full | Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| title_fullStr | Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| title_full_unstemmed | Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| title_short | Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| title_sort | efficient inhibition of amyloid fibrillation and cytotoxicity of α synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols |
| topic | GTPs GTPs-capped AgNPs Amyloid fibril Cytotoxicity Human insulin α-Synuclein |
| url | https://doi.org/10.1038/s41598-024-54464-4 |
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