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Molecular dynamics simulations are used to provide insights into the molecular mechanisms accounting for binding of amyloid fibrils to lipid bilayers and study the effect of cholesterol in this process. We show that electrostatic interactions play an important role in fibril-bilayer binding and cholesterol modulates this interaction. In particular, the interaction between positive residues and lipid head groups becomes more favorable in the presence of cholesterol. Consistent with experiments, we find that cholesterol enhances fibril-membrane binding.
This article was published in the following journal.
Name: The journal of physical chemistry. B
Human calcitonin (hCT) is a 32-residue peptide that aggregates to form amyloid fibrils under appropriate conditions. In this study, we investigated the effect of the intramolecular disulfide bond form...
Alzheimer's disease is a devastating pathology affecting an increasing number of individuals following the general rise in life expectancy. Amyloid peptide Aβ1-42 has been identified as one of the ma...
Protein amyloid fibrils are originally identified as pathological entities in a variety of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Recent studies have revealed ...
Using replica exchange with solute tempering all-atom molecular dynamics we studied the equilibrium binding of Abeta25-35 peptide to the ternary bilayer composed of an equimolar mixture of dimyristoyl...
Alzheimer's disease (AD) is characterized by the amyloid-beta peptide (Aβ) misfolding to form aberrant amyloid aggregates in the brain. Although recent evidence implicates that amyloid deposition in ...
Our proposed study aims to use 11C-acetate PET/CT to preliminarily test and validate methods for imaging astrocyte activation as an early indicator of neuroinflammation in Alzheimer's dise...
The overall purpose of this project is to improve the clinical outcomes of veterans with ischemic heart disease (IHD) through implementation of evidence-based lipid management, with a part...
The effect of fibrates on high density lipoprotein (HDL)-cholesterol levels is suggested to be mediated by its binding to peroxisome proliferator-activated receptor-g (PPARg). Upon ligand ...
This intervention study investigates the effects of various kale preparations (dietary supplements) on lipid status parameters. Within the study period of 8 weeks, three blood withdrawals ...
Systemic amyloidosis is a multi-system disease caused by extracellular deposition of insoluble amyloid fibrils in various tissues and organs, leading to progressive organ dysfunction. The ...
A type of extracellularly deposited substance composed of an amyloid protein and additional components including HEPARAN SULFATE PROTEOGLYCAN; LAMININ; COLLAGEN TYPE IV; SERUM AMYLOID P-COMPONENT; and APOLIPOPROTEINS E which together form characteristic amyloid fibrils. The core of amyloid fibrils is formed by the stacking of overlapping beta-pleated sheet domains of the amyloid protein. There are many different amyloid proteins that have been found forming the core of the fibrils in vivo. However, amyloid can be formed from any protein that exposes beta-pleated strand conformations during unfolding or refolding. A common characteristic of amyloid is the ability to bind such dyes as CONGO RED and thioflavine.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.
Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.
An ATP binding cassette transporter that functions primarily as a lipid and CHOLESTEROL exporter in MACROPHAGES. It may also function in intracellular lipid transport and homoeostasis.
Lipitor was the best selling drug in 2009, with the 2009 annual sales coming in at over $5m for its company, Pfizer Inc. Lipitor is the brand name for an atorvastatin calcium medication that is prescribed to lower cholesterol and triglycerides in the the...
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase 'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...