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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Autores principales:	Taisei Tanaka, Vipul V. Betkekar, Ken Ohmori, Keisuke Suzuki, Hideyuki Shigemori
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease amyloid β A-type procyanidin catechol human islet amyloid polypeptide type 2 diabetes Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/7773d17386fd4013be31a8374bb06bd0
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spelling	oai:doaj.org-article:7773d17386fd4013be31a8374bb06bd02021-11-25T18:39:29ZEvaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins10.3390/ph141111181424-8247https://doaj.org/article/7773d17386fd4013be31a8374bb06bd02021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1118https://doaj.org/toc/1424-8247The 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.Taisei TanakaVipul V. BetkekarKen OhmoriKeisuke SuzukiHideyuki ShigemoriMDPI AGarticleAlzheimer’s diseaseamyloid βA-type procyanidincatecholhuman islet amyloid polypeptidetype 2 diabetesMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1118, p 1118 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease amyloid β A-type procyanidin catechol human islet amyloid polypeptide type 2 diabetes Medicine R Pharmacy and materia medica RS1-441
spellingShingle	Alzheimer’s disease amyloid β A-type procyanidin catechol human islet amyloid polypeptide type 2 diabetes Medicine R Pharmacy and materia medica RS1-441 Taisei Tanaka Vipul V. Betkekar Ken Ohmori Keisuke Suzuki Hideyuki Shigemori Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins
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.
format	article
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
title	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_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_sort	evaluation of amyloid polypeptide aggregation inhibition and disaggregation activity of a-type procyanidins
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7773d17386fd4013be31a8374bb06bd0
work_keys_str_mv	AT taiseitanaka evaluationofamyloidpolypeptideaggregationinhibitionanddisaggregationactivityofatypeprocyanidins AT vipulvbetkekar evaluationofamyloidpolypeptideaggregationinhibitionanddisaggregationactivityofatypeprocyanidins AT kenohmori evaluationofamyloidpolypeptideaggregationinhibitionanddisaggregationactivityofatypeprocyanidins AT keisukesuzuki evaluationofamyloidpolypeptideaggregationinhibitionanddisaggregationactivityofatypeprocyanidins AT hideyukishigemori evaluationofamyloidpolypeptideaggregationinhibitionanddisaggregationactivityofatypeprocyanidins
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Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins

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