Objective
- To define common and newly designed apoE isoforms and domains involved in the interaction with its ligands.
- To produce these apoE isoforms in large quantities.
- To identify and characterize the interaction of these apoE isoforms with known and novel protein ligands in vitro and in vivo.
- To generate transgenic mice carrying genes that code for these apoE isoforms and amyloid precursor protein.
- To characterize these mice with respect to the development of atherosclerosis and Alzheimer's Disease.
By using interdisciplinary approaches, this project aims to study systematically how alterations in the structure of apoE affect its functions which lead to human disease. Special emphasis will be placed on the role of apoE in the pathogenesis of atherosclerosis and Alzheimer's Disease. Alteration in apoE which changes its interactions with lipoprotein receptors, the secreted proteins such as amyloid peptide b (Ab) or intracellular proteins (such as tau and other protein ligands) in the brain may lead to atherosclerosis and Alzheimer's Disease, respectively. Our knowledge on domains of apoE which are required for the binding of apoE to these receptors and other proteins are largely unknown.
Understanding the molecular mechanisms and pathophysiology of diseases caused by apoE mutations may provide effective intervention for the prevention of coronary heart diseases (CHD). In addition, variations at the apoE gene locus affects the risk for Alzheimer's disease (AD), the most common cause of dementia. Presently, no effective treatment for AD is known. Such treatment may become possible if we understand the molecular interactions between apoE and its intracellular or secreted protein ligands present in the brain. The major emphasis of this project will be placed on how the abnormal interactions of apoE with its ligands (Ab, tau, and other apoE ligands) and LRP contribute on the role of apoE in the pathogenesis of atherosclerosis and AD. This project will provide new insights on how genetic alteration may lead to age related neurodegenerative diseases (area 4.4) as well as to cardiovascular diseases (area 4.3) and may provide rational approaches towards the treatment of these conditions.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2333 CK LEIDEN
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.