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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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Detalles Bibliográficos
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
Descripción
Sumario: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.