Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme
The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 that has been linked to the neurodegeneration in Alzheimer’s disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE’s activity for the clearance...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1342 |
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| author | Qiuchen Zheng Micheal T. Kebede Bethany Lee Claire A. Krasinski Saadman Islam Liliana A. Wurfl Merc M. Kemeh Valerie A. Ivancic Charles E. Jakobsche Donald E. Spratt Noel D. Lazo |
| author_facet | Qiuchen Zheng Micheal T. Kebede Bethany Lee Claire A. Krasinski Saadman Islam Liliana A. Wurfl Merc M. Kemeh Valerie A. Ivancic Charles E. Jakobsche Donald E. Spratt Noel D. Lazo |
| author_sort | Qiuchen Zheng |
| collection | DOAJ |
| description | The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 that has been linked to the neurodegeneration in Alzheimer’s disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE’s activity for the clearance of Aβ42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE’s activity toward Aβ42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE’s activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity. |
| first_indexed | 2024-03-10T07:57:18Z |
| format | Article |
| id | doaj.art-a25d395273c14b41b4557b7a706bbf1a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T07:57:18Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-a25d395273c14b41b4557b7a706bbf1a2023-11-22T11:47:18ZengMDPI AGAntioxidants2076-39212021-08-01109134210.3390/antiox10091342Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading EnzymeQiuchen Zheng0Micheal T. Kebede1Bethany Lee2Claire A. Krasinski3Saadman Islam4Liliana A. Wurfl5Merc M. Kemeh6Valerie A. Ivancic7Charles E. Jakobsche8Donald E. Spratt9Noel D. Lazo10Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAGustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USAThe insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 that has been linked to the neurodegeneration in Alzheimer’s disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE’s activity for the clearance of Aβ42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE’s activity toward Aβ42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE’s activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity.https://www.mdpi.com/2076-3921/10/9/1342polyphenolsresveratrolepigallocatechin-3-gallateinsulin-degrading enzyme |
| spellingShingle | Qiuchen Zheng Micheal T. Kebede Bethany Lee Claire A. Krasinski Saadman Islam Liliana A. Wurfl Merc M. Kemeh Valerie A. Ivancic Charles E. Jakobsche Donald E. Spratt Noel D. Lazo Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme Antioxidants polyphenols resveratrol epigallocatechin-3-gallate insulin-degrading enzyme |
| title | Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme |
| title_full | Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme |
| title_fullStr | Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme |
| title_full_unstemmed | Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme |
| title_short | Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme |
| title_sort | differential effects of polyphenols on insulin proteolysis by the insulin degrading enzyme |
| topic | polyphenols resveratrol epigallocatechin-3-gallate insulin-degrading enzyme |
| url | https://www.mdpi.com/2076-3921/10/9/1342 |
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