Here are the Tyrosine modifications of insulin-degrading enzyme enable favorable control of substrate specificity for both Alzheimer's disease and type-2 diabetes mellitus journals presenting the latest research across various disciplines. From social sciences to technology, each article is expected to provide valuable insights to our readers.
Tyrosine modifications of pants, tyrosine modifications synonym, tyrosine modifications for gifted, tyrosine modifications for special education, tyrosine modifications meaning.
Tyrosine modifications of insulin-degrading enzyme enable favorable control of substrate specificity for both Alzheimer's disease and type-2 diabetes mellitus
Insulin-degrading enzyme (IDE) cleaves amyloid beta (Aβ), insulin, and other bioactive peptides. Because Aβ and insulin are closely related to Alzheimer's disease (AD) and type-2 diabetes mellitus (T2DM), respectively, IDE is a candidate drug target for treating both AD and T2DM. However, the activity of IDE has opposing effects, including decreasing AD risk by degrading Aβ and increasing T2DM risk by degrading insulin. The opposed substrate specificity is associated with the exo- and active sites containing Tyr314 and Tyr831 residues, the plausible modification targets for controlling substrate specificity. In this study, we used a tyrosine-specific modification regent, Cookson reagent (4-phenyl-1,2,4-triazoline-3,5-dione, PTAD), for IDE and examined the degradation activities on Aβ40 and insulin. Fifteen tyrosine residues, including Tyr314 and Tyr831, were modified by PTAD. After incubation with PTAD-modified IDE for 3 days, insulin remained intact, whereas Aβ40 was co mpletely degraded. This favorable change of substrate specificity was also observed in the mixture of Aβ40 and insulin, suggesting that tyrosine modification of IDE might be a therapeutic strategy for AD and T2DM. © 2024 The Author(s)
Authors : Hatakawa Y.; Takeuchi Y.; Lee S.H.; Oe T.
Source : Academic Press Inc.
Article Information
| Year | 2024 |
| Type | Article |
| DOI | 10.1016/j.bioorg.2024.107916 |
| ISSN | 00452068 |
| Volume | 153 |
You can download the article here
If You have any problem, contact us here