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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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/10/2444 |
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| author | Kenjiro Ono Mayumi Tsuji Tritia R. Yamasaki Giulio M. Pasinetti |
| author_facet | Kenjiro Ono Mayumi Tsuji Tritia R. Yamasaki Giulio M. Pasinetti |
| author_sort | Kenjiro Ono |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:37:36Z |
| format | Article |
| id | doaj.art-557de1d995d14776a56c908c2aa62ef7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:37:36Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-557de1d995d14776a56c908c2aa62ef72023-11-20T01:32:40ZengMDPI AGMolecules1420-30492020-05-012510244410.3390/molecules25102444Anti-aggregation Effects of Phenolic Compounds on α-synucleinKenjiro Ono0Mayumi Tsuji1Tritia R. Yamasaki2Giulio M. Pasinetti3Division of Neurology, Department of Internal Medicine, School of Medicine, Showa University, Tokyo 142-8666, JapanPharmacological Research Center, Showa University, Tokyo 142-8666, JapanDepartment of Neurology, University of Kentucky, Lexington, KY 40536, USADepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USAThe 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.https://www.mdpi.com/1420-3049/25/10/2444Parkinson’s diseaseα-synucleinphenolic compoundsgut microbiome |
| spellingShingle | Kenjiro Ono Mayumi Tsuji Tritia R. Yamasaki Giulio M. Pasinetti Anti-aggregation Effects of Phenolic Compounds on α-synuclein Molecules Parkinson’s disease α-synuclein phenolic compounds gut microbiome |
| 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 | Parkinson’s disease α-synuclein phenolic compounds gut microbiome |
| url | https://www.mdpi.com/1420-3049/25/10/2444 |
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