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Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process
Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multipl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495709/ https://www.ncbi.nlm.nih.gov/pubmed/36139781 http://dx.doi.org/10.3390/antiox11091711 |
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author | Sakalauskas, Andrius Janoniene, Agne Zvinys, Gediminas Mikalauskaite, Kamile Ziaunys, Mantas Smirnovas, Vytautas |
author_facet | Sakalauskas, Andrius Janoniene, Agne Zvinys, Gediminas Mikalauskaite, Kamile Ziaunys, Mantas Smirnovas, Vytautas |
author_sort | Sakalauskas, Andrius |
collection | PubMed |
description | Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multiple research articles have shown that the autoxidation of flavone is a critical factor for activating the inhibitory potential against the protein aggregation. Despite this, the structure of the newly-formed inhibitors is unknown. In this research, we examined the autoxidation products of 2′,3′-dihydroxyflavone that were previously shown to possess one of the most prominent inhibitory effects against amyloid-β aggregation. Their analysis using HPLC suggested the formation of polymeric molecules that were isolated using a 3 kDa cut-off. These polymeric structures were indicated as the most potent inhibitors based on protein aggregation kinetics and AFM studies. This revelation was confirmed using MALDI-TOF and NMR. We also show that active molecules have a tendency to reduce the Amyloid-β and α-synuclein aggregates toxicity to SH-SY5Y cells. |
format | Online Article Text |
id | pubmed-9495709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94957092022-09-23 Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process Sakalauskas, Andrius Janoniene, Agne Zvinys, Gediminas Mikalauskaite, Kamile Ziaunys, Mantas Smirnovas, Vytautas Antioxidants (Basel) Article Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multiple research articles have shown that the autoxidation of flavone is a critical factor for activating the inhibitory potential against the protein aggregation. Despite this, the structure of the newly-formed inhibitors is unknown. In this research, we examined the autoxidation products of 2′,3′-dihydroxyflavone that were previously shown to possess one of the most prominent inhibitory effects against amyloid-β aggregation. Their analysis using HPLC suggested the formation of polymeric molecules that were isolated using a 3 kDa cut-off. These polymeric structures were indicated as the most potent inhibitors based on protein aggregation kinetics and AFM studies. This revelation was confirmed using MALDI-TOF and NMR. We also show that active molecules have a tendency to reduce the Amyloid-β and α-synuclein aggregates toxicity to SH-SY5Y cells. MDPI 2022-08-30 /pmc/articles/PMC9495709/ /pubmed/36139781 http://dx.doi.org/10.3390/antiox11091711 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sakalauskas, Andrius Janoniene, Agne Zvinys, Gediminas Mikalauskaite, Kamile Ziaunys, Mantas Smirnovas, Vytautas Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title | Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title_full | Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title_fullStr | Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title_full_unstemmed | Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title_short | Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process |
title_sort | exploring the formation of polymers with anti-amyloid properties within the 2′3′-dihydroxyflavone autoxidation process |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495709/ https://www.ncbi.nlm.nih.gov/pubmed/36139781 http://dx.doi.org/10.3390/antiox11091711 |
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