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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2025-07-01
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| author | Makoto Mori Hiroto Nakano Sadao Hikishima Jota Minamikawa Daiki Muramatsu Yasuhiro Sakashita Tokuhei Ikeda Moeko Noguchi-Shinohara Kenjiro Ono |
| author_facet | Makoto Mori Hiroto Nakano Sadao Hikishima Jota Minamikawa Daiki Muramatsu Yasuhiro Sakashita Tokuhei Ikeda Moeko Noguchi-Shinohara Kenjiro Ono |
| author_sort | Makoto Mori |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-ac05573ce3de4f19b86ef8564fd75223 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Biomedicines |
| spelling | doaj-art-ac05573ce3de4f19b86ef8564fd752232025-08-20T04:00:49ZengMDPI AGBiomedicines2227-90592025-07-01137164910.3390/biomedicines13071649Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In VitroMakoto Mori0Hiroto Nakano1Sadao Hikishima2Jota Minamikawa3Daiki Muramatsu4Yasuhiro Sakashita5Tokuhei Ikeda6Moeko Noguchi-Shinohara7Kenjiro Ono8Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, JapanDepartment of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan<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.https://www.mdpi.com/2227-9059/13/7/16493-(4-hydroxy-3-methoxyphenyl) propionic acidamyloid β-proteinaggregationnucleationmature fibril Aβ seeds |
| spellingShingle | Makoto Mori Hiroto Nakano Sadao Hikishima Jota Minamikawa Daiki Muramatsu Yasuhiro Sakashita Tokuhei Ikeda Moeko Noguchi-Shinohara Kenjiro Ono Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro Biomedicines 3-(4-hydroxy-3-methoxyphenyl) propionic acid amyloid β-protein aggregation nucleation mature fibril Aβ seeds |
| title | Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro |
| title_full | Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro |
| title_fullStr | Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro |
| title_full_unstemmed | Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro |
| title_short | Inhibitory Effects of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid on Amyloid β-Peptide Aggregation In Vitro |
| title_sort | inhibitory effects of 3 4 hydroxy 3 methoxyphenyl propionic acid on amyloid β peptide aggregation in vitro |
| topic | 3-(4-hydroxy-3-methoxyphenyl) propionic acid amyloid β-protein aggregation nucleation mature fibril Aβ seeds |
| url | https://www.mdpi.com/2227-9059/13/7/1649 |
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