Apolipoproteins and Amyloid Formation in Atheroma

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/350229

Funding Status
Closed

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Funded Activity Summary

We propose to study the poorly understood, disease-associated process of amyloid formation, using a sensitive and reproducible model developed in our laboratory. Amyloid deposits are a feature of several neurodegenerative and metabolic disorders such as Alzheimer's and Parkinson's disease and are also common in atherosclerotic plaque or atheroma. They are composed of tangled networks of fibrillar proteins together with several non-fibrillar proteins and proteoglycans. Atherosclerotic plaques typically consist of fibrous proteins, lipids and foam cells derived from macrophages via receptor-mediated uptake of oxidized low density lipoproteins. Our model system is based on the formation of amyloid fibrils from apolipoprotein (apo) C-II which accumulates in atherosclerotic plaques where it co-localizes with serum amyloid P component, a marker of amyloid fibrils. ApoC-II is a component of plasma lipoproteins and an important activator of the enzyme lipoprotein lipase, which functions in the transport and distribution of triacylglycerols to tissues. We have shown that apoC-II (79 amino acids) readily forms amyloid fibrils under lipid-free conditions, adopting a cross-beta sheet structure that reacts with the amyloid stains thioflavin T and Congo Red. The formation and properties of apoC-II amyloid fibrils and the amyloid-like properties of oxidized lipoproteins are the subject of the present proposal. We will characterize the effects of lipids and oxidation on the rate of formation and the properties of apoC-II amyloid fibrils. We will also study the effects of oxidation on the amyloid-like properties of lipoproteins and their interactions with serum amyloid P component and cell surface receptors.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $439,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

age-related diseases | amyloid | atherosclerosis | cardiovascular disease | coronary heart disease | hypercholesterolemia | lipoproteins | protein chemistry | protein-protein interaction

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