Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins
The number of people worldwide suffering from Alzheimer’s disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates...
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MDPI AG
2021-10-01
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| Series: | Pharmaceuticals |
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| author | Taisei Tanaka Vipul V. Betkekar Ken Ohmori Keisuke Suzuki Hideyuki Shigemori |
| author_facet | Taisei Tanaka Vipul V. Betkekar Ken Ohmori Keisuke Suzuki Hideyuki Shigemori |
| author_sort | Taisei Tanaka |
| collection | DOAJ |
| description | The number of people worldwide suffering from Alzheimer’s disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins <b>1</b>–<b>7</b> and their substructures <b>8</b> and <b>9</b>, by conducting structure–activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds <b>1</b>–<b>6</b> exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound <b>7</b>, without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases. |
| first_indexed | 2024-03-10T05:10:00Z |
| format | Article |
| id | doaj.art-7773d17386fd4013be31a8374bb06bd0 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:10:00Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7773d17386fd4013be31a8374bb06bd02023-11-23T00:55:30ZengMDPI AGPharmaceuticals1424-82472021-10-011411111810.3390/ph14111118Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type ProcyanidinsTaisei Tanaka0Vipul V. Betkekar1Ken Ohmori2Keisuke Suzuki3Hideyuki Shigemori4Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, JapanDepartment of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, JapanDepartment of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, JapanDepartment of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, JapanFaculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, JapanThe number of people worldwide suffering from Alzheimer’s disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins <b>1</b>–<b>7</b> and their substructures <b>8</b> and <b>9</b>, by conducting structure–activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds <b>1</b>–<b>6</b> exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound <b>7</b>, without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases.https://www.mdpi.com/1424-8247/14/11/1118Alzheimer’s diseaseamyloid βA-type procyanidincatecholhuman islet amyloid polypeptidetype 2 diabetes |
| spellingShingle | Taisei Tanaka Vipul V. Betkekar Ken Ohmori Keisuke Suzuki Hideyuki Shigemori Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins Pharmaceuticals Alzheimer’s disease amyloid β A-type procyanidin catechol human islet amyloid polypeptide type 2 diabetes |
| title | Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins |
| title_full | Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins |
| title_fullStr | Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins |
| title_full_unstemmed | Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins |
| title_short | Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins |
| title_sort | evaluation of amyloid polypeptide aggregation inhibition and disaggregation activity of a type procyanidins |
| topic | Alzheimer’s disease amyloid β A-type procyanidin catechol human islet amyloid polypeptide type 2 diabetes |
| url | https://www.mdpi.com/1424-8247/14/11/1118 |
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