Phenolic Acids Commonly Found in Natural Products Modulate Protein Aggregation in Neurodegeneration Models.

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 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.