Objective
The major motor disabilities of Parkinson's disease (PD) are associated with the progressive loss of dopaminergic neurons in the substantia nigra. The physiological changes and biochemical pathways involved in the selective demise of these neuronsare unclear. Survival of the dopaminergic precursor neurons during differentiation requires the function of NR4A2, a ligand independent nuclear receptor. Mutations in NR4A2 have been discovered in patients with familial PD. The mutations resulted in a marked decrease in NR4A2 mRNA levels in transfected cell lines and in lymphocytes of affected individuals.
Additionally, the mutations in NR4A2 affected the transcription of the gene encoding Tyrosine Hydroxylase (TH), an enzyme required for dopamine biosynthesis. Endogenous ligands that regulate RXR function as well as synthetic H gands that activate NR4A2-RXR heterodimers have been shown to mediate RXR ligand-induced signalling in neuronal cells. TheseRXR ligands require the presence of NR4A2 and increase the number of surviving dopaminergic cells and other neurons.
It is speculated that NR4A2, as a transcription factor, controls the expression of neuroprotective factors possibly by associating with RXR. In this proposal we aim to identify such factors. Since the number and the identity of the genes whose expression is controlled by NR4A2 and/or NR4A2/RXR heterodimers are unknown we propose to identify these genes and determine the function of the ones that mediate neuroprotective effects. In addition, we propose to clarify the transcriptional relationship of NR4A2 to the other genes that have been linked to familial PD including alpha-synuclein, parkin, DJ1, UCHL1 and PINK. The results of our experiments may reveal the factors that lead to the prevention or perhaps reversal of the major motor disabilities of PD by increasing dopaminergic cell survival.
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 physiology pathophysiology
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology parkinson
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-12
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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
ATHENS
Greece
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.