Complex and Multidimensional Lipid Raft Alterations in a Murine Model of Alzheimer's Disease

Author:

Chadwick Wayne1,Brenneman Randall12,Martin Bronwen3,Maudsley Stuart1

Affiliation:

1. Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA

2. Miller School of Medicine, University of Miami, Miami, FL 33124, USA

3. Metabolism Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA

Abstract

Various animal models of Alzheimer's disease (AD) have been created to assist our appreciation of AD pathophysiology, as well as aid development of novel therapeutic strategies. Despite the discovery of mutated proteins that predict the development of AD, there are likely to be many other proteins also involved in this disorder. Complex physiological processes are mediated by coherent interactions of clusters of functionally related proteins. Synaptic dysfunction is one of the hallmarks of AD. Synaptic proteins are organized into multiprotein complexes in high-density membrane structures, known as lipid rafts. These microdomains enable coherent clustering of synergistic signaling proteins. We have used mass analytical techniques and multiple bioinformatic approaches to better appreciate the intricate interactions of these multifunctional proteins in the 3xTgAD murine model of AD. Our results show that there are significant alterations in numerous receptor/cell signaling proteins in cortical lipid rafts isolated from 3xTgAD mice.

Funder

National Institutes of Health

Publisher

Hindawi Limited

Subject

Behavioral Neuroscience,Cellular and Molecular Neuroscience,Cognitive Neuroscience,Neurology (clinical),Neurology,Aging,General Medicine

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