# Phenolic Acids Commonly Found in Natural Products Modulate Protein Aggregation in Caenorhabditis elegans Neurodegeneration Models

## TL;DR

This study explores how phenolic acids from natural products can reduce protein aggregation in worm models of neurodegenerative diseases like Alzheimer's and Parkinson's.

## Contribution

The novel contribution is identifying specific phenolic acids that effectively reduce protein aggregation in multiple C. elegans models of neurodegeneration.

## Key findings

- High concentrations of caffeic, ferulic, and gallic acids reduced β-amyloid-induced paralysis by up to 32%.
- Gallic acid showed the strongest reduction in polyQ aggregation (47%) compared to other acids.
- Caffeic acid alone reduced α-synuclein aggregation, suggesting potential neuroprotective effects in mammals.

## Abstract

Abnormal protein accumulation is frequently associated
with the gradual degeneration of the central nervous system, which
results in the development and progression of several neurodegenerative
diseases (NDs). Since the incidence of ND is on the rise, their effects
represent a substantial psychological and economic burden. As we advance
in understanding human aging mechanisms, it is desirable to accelerate
the discovery of molecules that can modulate human aging and perhaps
postpone the onset of age-related disease. Therefore, uncovering compounds
that can prevent the formation of protein aggregates should be a priority
in the aging research field. Phenolic acids are organic compounds
found in many natural products, such as vegetables and fruits. These
compounds have been shown to have potential neuroprotective benefits.
However, its effects on protein aggregation related to neurodegeneration
processes are still not clear. In this study, we thoroughly explored
the ability of four phenolic acids: caffeic (CA), p-coumaric (p-CoA),
ferulic (FA), and gallic (GA) acids to prevent protein aggregation
in three Caenorhabditis elegans models
of human neurodegeneration, such as Alzheimer’s disease, Huntington’s
disease, and Parkinson’s disease. We found that high CA, p-CoA,
FA, and GA concentrations reduce the β-amyloid-aggregation-induced
paralysis phenotype by up to 32%. Also, high CA, FA, and GA concentrations
decreased paralysis percentage and polyQ aggregations by 25, 26, and
47%, respectively. Interestingly, high concentrations of p-CoA reduced
polyQ aggregation but not the percentage of protein aggregation-induced
paralysis. Additionally, only high concentrations of CA, along with
lower concentrations of FA and GA, demonstrated the potential to reduce
α-synuclein
aggregation. Our findings suggest that CA, FA, and GA are worthy candidates
for acting as neuroprotectors in mammals.