Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro

TL;DR

This study shows that HMPA, a polyphenol metabolite, can inhibit the aggregation of amyloid-beta peptides, which are linked to dementia.

Contribution

The study demonstrates HMPA's novel inhibitory effects on both nucleation and elongation phases of Aβ42 aggregation.

Findings

ThT assays showed HMPA inhibits nucleation and elongation phases of Aβ aggregation.

Electron microscopy revealed shorter Aβ42 fibrils in the presence of HMPA.

The EC50 of HMPA for low-molecular-weight Aβ42 was 5–6 mM.

Abstract

Objectives: The compound 3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a terminal metabolite derived from polyphenol compounds. It has been studied for its potential to support brain health indirectly through its anti-oxidant effects and ability to enhance the gut environment; however, its role in dementia pathogenesis is unclear. Therefore, the aim of this study was to evaluate how HMPA inhibits Aβ42 aggregation in vitro. Methods: We examined the inhibitory effects of HMPA on amyloid-β protein (Aβ) aggregation using a thioflavin T (ThT) assay and electron microscopy (EM). Results: ThT assays demonstrated that HMPA inhibited both the nucleation and elongation phases of Aβ aggregation. Additionally, EM of low-molecular-weight (LMW) Aβ42 in the presence of HMPA demonstrated shorter fibrils compared to those formed without HMPA. The EC50 of HMPA in LMW Aβ42 was 5–6 mM. Conclusions: These findings indicate that, similar to several polyphenol compounds such as myricetin and rosmarinic acid, HMPA may inhibit Aβ pathogenesis, although it requires a fairly high concentration in vitro. These findings suggest the potential of HMPA as a lead compound for modulating Aβ-related neurodegeneration.

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