Objective
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, caused by degeneration of dopaminergic neurons in the substantia nigra. While the cause of the more frequent sporadic forms of PD remains unknown, the recent discovery of mutations in genes causing rare familial forms of PD provide a basis for better understanding of the molecular pathogenesis of the disease.
One of these genes, LRRK2, encodes a protein with multiple predicted functional domains. Point mutations leading to auto somal-dominant PD have been found in all identified domains. Interestingly, mutations in the kinase domain of LRRK2 increase its (auto)kinase activity, inducing neuronal degeneration in cultured cells.
These results point to a gain of function phenotype l inked to these mutations, which is in line with the autosomal dominant feature of the known LRRK2 mutations in PD. In spite of this exciting recent progress, it remains unclear what aspects of LRRK2 function are relevant toward PD in vivo. Based on our cur rent knowledge we hypothesize that LRRK2 is a multifunctional protein that is an important regulator of the function of proteins central to PD. LRRK2 mutations interfere with this interaction, leading to degeneration of dopaminergic neurons in the substant ia nigra. To test this hypothesis, we propose to generate an in vivo model for PD linked LRRK2 mutations.
Using a state-of-the-art recombinase mediated cassette insertion method we will introduce specific LRRK2 mutations in mice. The strength of our approach is that we use minimal changes in the LRRK2 genetic locus, and it will allow us to study the effect of the mutation directly on its interaction with unknown proteins in the cells and tissue context that is relevant to the disease. We are confident that these studies will be an important step towards elucidation of the molecular pathways of PD pathogenesis and potential targets for therapeutic intervention.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology parkinson
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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.
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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
See other projects for this call
Funding Scheme
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.
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
ZWIJNAARDE
Belgium
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.