Surface plasmon resonance for the analysis of beta-amyloid interactions and fibril formation in Alzheimer's disease research.
Alzheimer's disease (AD) is a neurodegenerative disorder characterised by the accumulation of amyloid deposits, the major component of which is a 4 kDa polypeptide known as beta-amyloid protein (ABeta). Identifying the mechanism underlying the formation of Abeta and the pathways that lead to its toxicity is crucial to understanding the mechanism of AD and addressing the urgent need for new and effective treatments for AD. The accumulation of ABeta is the result of a complex interplay between genetic and environmental factors that affect the generation, clearance and aggregation of the peptide. Because of its propensity to aggregate, ABeta builds up in the brain and assembles into amyloid fibrils, ultimately creating amyloid plaques (APs) and cerebral amyloid angiopathy (CAA). Abeta has been shown to interact with a number of intracellular and extracellular molecules, but the relative contribution of these interactions to the toxicity of Abeta is not well understood. A critical step in characterising the importance of these interactions is the ability to measure both the affinity and kinetics of these interactions. Surface plasmon resonance (SPR) spectroscopy has become a widely used technique to study molecular interactions such as antibody-antigen, DNA-DNA, DNA-protein, protein-protein, receptor-ligand and peptide- and protein-membrane interactions. This article reviews the application of SPR to the study of the molecular interactions associated with AD and how this information enhances our molecular understanding of ABeta -mediated toxicity.
Aguilar
Marie-Isabel
MI
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia. mibel.aguilar@med.monash.edu.au
Small
David H
DH
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)