ArticleBiophysical journal2016
The Role of Cholesterol in Driving IAPP-Membrane Interactions.
Article in Biophysical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 85 citations in OpenAlex.
- A Metabolomics-Based Strategy for Identifying Endogenous Inhibitors of IAPP Aggregation.Metabolites · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Investigating the Design of ssPalmO-Derived Lipid Nanoparticles for mRNA Delivery Applications Using Molecular Dynamics Simulations.ACS omega · 2025Article
- Critical micellar concentration determination of pure phospholipids and lipid-raft and their mixtures with cholesterol.Proteins · 2025Article
- Modulation of Biological Membranes Using Small-Molecule Compounds to Counter Toxicity Caused by Amyloidogenic Proteins.Membranes · 2024Review
- Elucidation of molecular mechanisms by which amyloid βBiochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- The influence of zwitterionic and anionic phospholipids on protein aggregation.Biophysical chemistry · 2024Review
- Antiviral activity of the host defense peptide piscidin 1: investigating a membrane-mediated mode of action.Frontiers in chemistry · 2024Article
- Fluorescence Resonance Energy Transfer to Detect Plasma Membrane Perturbations in Giant Plasma Membrane Vesicles.Bio-protocol · 2023Article
- Exploring the Role of Anionic Lipid Nanodomains in the Membrane Disruption and Protein Folding of Human Islet Amyloid Polypeptide Oligomers on Lipid Membrane Surfaces Using Multiscale Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2023Article
- Article
- Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases.Computational and structural biotechnology journal · 2023Review
- Fibril elongation by human islet amyloid polypeptide is the main event linking aggregation to membrane damage.BBA advances · 2023Article
- All-atom molecular dynamics simulations of the combined effects of different phospholipids and cholesterol content on electroporation.RSC advances · 2022Article
- Article
- Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.Molecules (Basel, Switzerland) · 2022Review
- Conformational Tuning of Amylin by Charged Styrene-Maleic-Acid Copolymers.Journal of molecular biology · 2022Article
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- The Effect of Cholesterol on Membrane-Bound Islet Amyloid Polypeptide.Frontiers in molecular biosciences · 2021Article
- Sub-stoichiometric inhibition of IAPP aggregation: a peptidomimetic approach to anti-amyloid agents.RSC chemical biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our knowledge of the molecular events underlying type 2 diabetes mellitus-a protein conformational disease characterized by the aggregation of islet amyloid polypeptide (IAPP) in pancreatic β cells-is limited. However, amyloid-mediated membrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intense research. In particular, membrane cholesterol content varies with aging and consequently with adverse environmental factors such as diet and lifestyle, but its role in the development of the disease is controversial. In this study, we employ a combination of experimental techniques and in silico molecular simulations to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption. We show that if anionic POPC/POPS vesicles are used as model membranes, cholesterol has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer. In addition, cholesterol inhibits membrane damage by amyloid-induced poration on membranes, but enhances leakage through fiber growth on the membrane surface. Conversely, if 1:2 DOPC/DPPC raft-like model membranes are used, cholesterol accelerates fiber growth. Next, it enhances pore formation and suppresses fiber growth on the membrane surface, leading to leakage. Our results highlight a twofold effect of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabetes mellitus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.