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Abstract

The correlation between lifestyle choices, dietary habits, and the onset of chronic illnesses has been well-established. With the increasing population and life expectancy in the United States, there's a heightened susceptibility to age-related neurodegenerative conditions. Parkinson’s disease (PD) is one such condition, characterized by factors including dopaminergic neuron degeneration, increased inflammation, and abnormal α-synuclein protein accumulation. While the exact causes of PD remain elusive, both environmental and genetic susceptibility factors are believed to play a role. Emerging evidence suggests that disturbances in the gut microbiome and resulting metabolites may contribute to PD pathology, prompting intensified research into the mechanisms of gut-related inflammation and α-synuclein protein aggregation. Plant polyphenols, found abundantly in various medicinal plants, have shown promise in laboratory studies by disrupting aberrant protein aggregation, influencing cellular signaling, and regulating gut microbiome imbalances. Epidemiological evidence suggests that regular intake of plant polyphenols, namely tea catechins, could reduce the risk of PD by shielding neurons, although clinical trials are still limited. The biological effects of tea catechins can vary, prompting interest in assessing their dietary significance. We hypothesized that tea catechin intake would modify the composition of the gut microbiota and gut-microbiota dependent metabolic pathways. Resulting microbes and the specific metabolites would then lead to the enhancement of the neuroprotective effects of tea catechins by attenuating α-synuclein aggregation and circulation. As such, we aimed to investigate the molecular mechanisms of tea catechins in a transgenic PD mouse model that overexpresses mutant human A53T α-synuclein protein; investigate whether tea catechin altered gut microbiome could contribute to lowering α-synuclein aggregation in vivo following a 90-day tea catechin treatment; and to combine metagenomics with metabolomics to investigate the impact of tea catechins on the composition and function of the gut microbiota in a transgenic PD mouse model.

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