Objective
One of the major pathological hallmarks of Parkinson´s disease (PD) is the progressive loss of specific dopaminergic projection neurons, especially those located in the substantia nigra pars compacta. The neurodegeneration is accompanied by the presence of cytoplasmic inclusions called Lewy bodies, which invariably contain the α-synuclein (α-syn) protein as a major component. Aggregation of α-syn in the brains of PD patients has attracted much attention also because point mutations in the α-syn gene were found to cause rare dominantly inherited form of PD. Although the precise mechanism of the selective vulnerability of dopaminergic neurons in the midbrain remains unknown, there is increasing evidence that multiple pathogenic factors including impaired handling of cytoplasmic dopamine (DA), elevated levels of reactive oxygen species (ROS) and abnormal phosphorylation of α-syn could cause selective death of these cells via the accumulation of soluble neurotoxic α-syn species. Building on the know how and expertise of the host lab I propose to study 1) the pathogenic interaction of DA/α-syn by genetically increasing cytoplasmic DA levels in the viral vector mediated α-syn overexpression model, which I propose would result in a more pronounced neurodegeneration; 2) the role of ROS by upregulation of the enzyme methionine sulfoxide reductase A (known to prevent oxidative damage by scavenging of ROS). I hypothesize that expression of this enzyme should result in protection of dopaminergic neurons in the α-syn overexpression model; and 3) the consequences of increased Ser 129 phosphorylation of α-syn by overexpressed polo like kinases, which should modify neurotoxicity in the viral vector mediated α-syn overexpression model. These 3 approaches could give important clues for understanding the mechanisms underlying the selective neurodegeneration in PD and thus lead to the development of novel therapeutic strategies in PD.
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.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology neurodegenerative diseases parkinson
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-IEF
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Funding Scheme
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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
22100 LUND
Sweden
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.