Objective
NMDA receptors (Nadirs) are implicated in many neuropsychological and neuropath logical processes including schema, epilepsy and schizophrenia. They are heteromeric gated-gated ion channels likely composed of two NR1 and two NR2 subunits. Extra cellular agents including Zn. Co-released at some synapses with glutamate modulate nadirs, Zn is a potentially important physiological regulator of Malfunction. The NR2 subunit subtype, NR2A being the most sensitive, determines Zn affinity for Nadirs. InNR2A the high-affinity Zn binding site maps to the N-terminal domain, whilst in NR2B the homologous domain binds the neuroprotectant ifenprodil, a non-competitive antagonist specific for NR2B-containing NMDARs. Demodulator N-terminal domains therefore present potentially interesting pharmaceutical targets. To date, functional studies on recombinant Nadirs have centred on receptors containing only one NR2 subunit subtype, however, biochemical evidence suggests that many native Nadirs contain two subtypes of NR2.Using mutated receptors we will isolate populations of recombinant "triplet" receptors containing two different subtypes of NR2. Their function will be assessed using electrophysiological techniques, allowing us to answer several key questions. Firstly, "triplets" containing a wild-type NR2A subunit and a NR2A subunit lacking the functional high-affinity Zn binding site will be used to determine the functional stoichiometry of the Zn inhibition. Secondly, using "triplets" containing both a NR2A and a NR2B, NR2C or NR2D subunit, we will assess the functional properties of recombinant Nadirs containing two types of NR2 subunit. Of particular interest is the interaction in NR2A/NR2B "triplets" between Zn and ifenprodil. Finally, to assess the physiological relevance of triplet" Nadirs, we will compare the properties of recombinant "triplets" and native receptors found in brain regions where more than one type of#
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 epilepsy
- medical and health sciences clinical medicine psychiatry schizophrenia
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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-5
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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
PARIS
France
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.