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Anti-aggregation Effects of Phenolic Compounds on α-synuclein

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increas...

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Autores principales: Ono, Kenjiro, Tsuji, Mayumi, Yamasaki, Tritia R., Pasinetti, Giulio M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288075/
https://www.ncbi.nlm.nih.gov/pubmed/32456274
http://dx.doi.org/10.3390/molecules25102444
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author Ono, Kenjiro
Tsuji, Mayumi
Yamasaki, Tritia R.
Pasinetti, Giulio M.
author_facet Ono, Kenjiro
Tsuji, Mayumi
Yamasaki, Tritia R.
Pasinetti, Giulio M.
author_sort Ono, Kenjiro
collection PubMed
description The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies.
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spelling pubmed-72880752020-06-17 Anti-aggregation Effects of Phenolic Compounds on α-synuclein Ono, Kenjiro Tsuji, Mayumi Yamasaki, Tritia R. Pasinetti, Giulio M. Molecules Review The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies. MDPI 2020-05-24 /pmc/articles/PMC7288075/ /pubmed/32456274 http://dx.doi.org/10.3390/molecules25102444 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ono, Kenjiro
Tsuji, Mayumi
Yamasaki, Tritia R.
Pasinetti, Giulio M.
Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title_full Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title_fullStr Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title_full_unstemmed Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title_short Anti-aggregation Effects of Phenolic Compounds on α-synuclein
title_sort anti-aggregation effects of phenolic compounds on α-synuclein
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288075/
https://www.ncbi.nlm.nih.gov/pubmed/32456274
http://dx.doi.org/10.3390/molecules25102444
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