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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...

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Autores principales: Sakalauskas, Andrius, Janoniene, Agne, Zvinys, Gediminas, Mikalauskaite, Kamile, Ziaunys, Mantas, Smirnovas, Vytautas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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