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Content archived on 2024-06-10

Mechanisms of Intercellular Signalling in Alzheimer's Disease : The Role of Apolipoprotein E

Objective

Elucidation of the role of apo E and its receptors in inter- and intracellular signalling within the AD brain. Given that apo E has a crucial role in the local redistribution of lipids during nerve injury and repair, the research will unravel major aspects of the pathophysiology of central nervous tissue damage and regeneration. The role of lipoprotein receptors and lactoferrin will address immunological mechanisms of neurological disorders.

To elucidate pathogenesis of Alzheimer's disease, advantage is taken of the participants expertise in lipoprotein metabolism, brain cell metabolism and signal transduction in nerve cells. The factors governing the regulation of the expression of apoE (and variant forms E2, E2, and E4) in astrocytes will be explored. A set of cells to be characterised for apoE metabolism and the receptors therefore (C6 glial cells, a glia-like cell line (U373)) and astrocyte rich primary cultures, neuron like cell lines (PC12), hNT-neurons and hippocampal neurons of Banker-cultures will be characterised and distributed.
These tools will be used to characterise in detail the interaction of variant forms of apo E with constituents of the extracellular matrix in the nervous system such as A4/beta and heparan sulphate proteoglycans. They will allow to define the receptor mediated pathways and their regulation serving the delivery of variant forms of apo E into glial and neuronal cells. As a result the effects of variant forms of apo E on the processing of normal and mutant amyloid precursor proteins as well as possible intracellular effects of apo E on the structure and function of the cytoskeleton, can be elucidated. Results hinting that apo E variants differentially influence neuronal survival will finally direct research towards therapeutic studies.

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CON - Coordination of research actions

Coordinator

Universität Wien
EU contribution
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Address
10,Waehringerstrasse
1090 VIENNA
Austria

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Total cost

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