Exploring the mechanism of beta-amyloid toxicity attenuation by multivalent sialic acid polymers through the use of mathematical models.
beta-Amyloid peptide (A beta), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the A beta-neuronal membrane interaction plays a role in the mechanism of A beta toxicity. More specifically, it is thought that A beta interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have used a number of different sialic acid compounds of different valency or number of sialic acid moieties per molecule to attenuate A beta toxicity in a cell culture model. In this work, we proposed various mathematical models of A beta interaction with both the cell membrane and with the multivalent sialic acid compounds, designed to act as membrane mimics. These models allow us to explore the mechanism of action of this class of sialic acid membrane mimics in attenuating the toxicity of A beta. The mathematical models, when compared with experimental data, facilitate the discrimination between different modes of action of these materials. Understanding the mechanism of action of A beta toxicity inhibitors should provide insight into the design of the next generation of molecules that could be used to prevent A beta toxicity associated with AD.
Cowan
Christopher B
CB
Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Patel
Dhara A
DA
Good
Theresa A
TA
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D040761:Biomimetic Materials / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008954:Models, Biological; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D019158:N-Acetylneuraminic Acid