It has been suggested that the connection between amyloidogenic diseases is related to the interactions between aggregates of amyloids, which are related to type 2 diabetes and Parkinson's disease. Herein, we illustrate the interactions between amylin oligomers and non-amyloid β component (NAC) oligomers. Using molecular dynamics simulations and statistical calculations, we studied the mechanisms through which NAC oligomers interact with amylin oligomers to form NAC-amylin hetero-oligomers. Our simulations have shown that there are more than one possible pathways, which form the NAC-amylin hetero-oligomers. Our structural analyses demonstrate that the interactions in the NAC-amylin hetero-oligomers do not affect the structural features of the NAC oligomers, but they do stabilize the structures of the amylin oligomers. Taken together, our results strongly support the hypothesis that NAC oligomers may interact with amylin oligomers through several pathways, of which some pathways are more preferred because of the structural stability of the cross-seeding NAC-amylin oligomers.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jpcb.6b07731 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nitration of Tyr37 alters the aggregation pathway of hIAPP and enhances its cytotoxicity.
Int J Biol Macromol
January 2025
Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China. Electronic address:
The amyloid aggregation of hIAPP and the increased level of oxidative stress are closely related to the occurrence and development of type 2 diabetes (T2D). Protein tyrosine nitration is a common post-translational modification under oxidative stress conditions. We previously found that tyrosine nitrated hIAPP (3-NT-hIAPP) has higher cytotoxicity than wild type hIAPP.
View Article and Find Full Text PDFEffect of Meroterpenoids from Sargassum macrocarpum on the Inhibition of Amyloid Polypeptide Aggregation.
Biol Pharm Bull
December 2024
Institute of Life and Environmental Sciences, University of Tsukuba.
Amyloid polypeptide aggregation is considered one of the factors involved in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), and the number of affected patients increases as the population ages. Amyloid β (Aβ) found in the brain of patients with AD and human islet amyloid polypeptide (hIAPP) found in the pancreas of patients with T2D are thought to be cytotoxic during the aggregation process, especially the low-molecular-weight oligomers that are aggregation intermediates. In this study, meroterpenoids isolated and structurally determined from the brown alga Sargassum macrocarpum were evaluated for their ability to inhibit hIAPP aggregation.
View Article and Find Full Text PDFLipids determine the toxicity of human islet polypeptide aggregates in vivo.
J Biol Chem
November 2024
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, United States. Electronic address:
The onset and progression of type 2 diabetes is linked to the accumulation and aggregation of human islet amyloid polypeptide (hIAPP) in the pancreas. Amyloid oligomers and fibrils formed as a result of such aggregation exert high cytotoxicity. Although some pieces of evidence suggest that lipids could alter the rate of hIAPP aggregation, the effect of lipids on the aggregation properties of this peptide remains unclear.
View Article and Find Full Text PDFInfluence of anti-fibrillation TNGQ peptide and rutin combination on β-cell cytoprotective effects against IAPP-induced cell death and oxidative stress.
Biochem Biophys Res Commun
December 2024
School of Nutrition Sciences, Health Sciences, University of Ottawa, Ottawa, K1H 8M5, Canada; Department of Chemistry and Biomolecular Sciences, Science, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada; University Food Properties and Nutrient Bioavailability, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada. Electronic address:
Article Synopsis
- Type 2 diabetes is linked to IAPP fibrillation, which damages pancreatic β-cells through oxidative stress and membrane disruption.
- Rutin, a plant polyphenol, and certain bioactive peptides (TNGQ, MANT, YMSV) show promise as inhibitors for IAPP fibrillation.
- The study found that combining rutin with TNGQ significantly reduced IAPP fibrillation and related cell toxicity, suggesting potential for creating new anti-diabetic nutraceuticals.
Analysis of dimer and trimer complexes of the non-amyloidogenic rat islet amyloid polypeptide 21-37 by electrospray ionization-tandem mass spectrometry.
Eur J Mass Spectrom (Chichester)
October 2024
Department of Chemistry and Bioscience, Kumoh National Institute of Technology, Gumi, Republic of Korea.
The dimer and trimer structures of the non-amyloidogenic rat islet amyloid polypeptide 21-37 peptide, formed in an HO/CHOH (1% CHCOOH) solution were investigated using electrospray ionization-tandem mass spectrometry (ESI-MS/MS). The dissociation of monomers, dimers, and trimers was investigated by MS/MS using collision-induced dissociation. The peptide bond dissociation between L and P was mainly observed in the tandem mass spectra of the monomers and oligomers, regardless of the parent ion charge state.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!