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

<b>Objectives</b>: 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 environ...

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Main Authors: Makoto Mori, Hiroto Nakano, Sadao Hikishima, Jota Minamikawa, Daiki Muramatsu, Yasuhiro Sakashita, Tokuhei Ikeda, Moeko Noguchi-Shinohara, Kenjiro Ono
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/7/1649
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Summary:<b>Objectives</b>: 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. <b>Methods</b>: We examined the inhibitory effects of HMPA on amyloid-β protein (Aβ) aggregation using a thioflavin T (ThT) assay and electron microscopy (EM). <b>Results</b>: 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 EC<sub>50</sub> of HMPA in LMW Aβ42 was 5–6 mM. <b>Conclusions</b>: 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.
ISSN:2227-9059