Year: 2020
Type: article
Abstract: 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.
Source: Molecules
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Funders: Office of Dietary Supplements, U.S. Department of Veterans Affairs, Japan Agency for Medical Research and Development, National Institutes of Health, Japan Society for the Promotion of Science, National Center for Advancing Translational Sciences, National Center for Complementary and Integrative Health
Awards: G2980429159, G3120110074, G4364743598, G5730785774, Study on the toxic mechanism of high-molecular A-beta oligomers focusing on membrane damage, G8144194998, Search for health food ingredients to prevent the onset of Alzheimer's disease targeting inhibition of amyloid B toxicity, G8900914772, G9000129450, G9000259622, Institutional Career Development Core
OpenAlex ID: W3027550282