Objective
To study mechanisms of GDNF signal transduction, and the ligand-receptor interactions of normal Ret, different RET isoforms and mutants found in Hirschsprung's disease and MEN2 patients.
To investigate biological roles of GDNF and other family members and their receptors in the development and maintenance of major areas and pathways of the peripheral and central nervous systems, including those affected in human neurological disorders.
To screen for mutations in the GDNF gene in pediatric developmental disorders, such as Hirschsprung's disease and neurointestinal dysplasias, and in Parkinson's disease.
To identify and characterize novel receptors for GDNF and other family members.
Glial cell line-derived neurotrophic factor (GDNF) maintains central dopaminergic, noradrenergic and motorneurons, as well as various populations of peripheral neurons. GDNF is therefore a most promising candidate for therapeutics of acute nerve injury and chronic neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis. A recent collaborative effort from the partner laboratories has established that c-RET, an orphan receptor tyrosine kinase that plays important roles in mammalian development and human disease, is a functional receptor for GDNF. Germ-line mutations of c-ret contribute to developmental abnormalities of the intestinal innervation in a fraction of cases of Hirschsprung's disease or congenital intestinal aganglionosis, and they have also been found in patients with multiple endocrine neoplasia (MEN) type 2 and medullary thyroid carcinoma. The general objective of this proposal is to create a collaborative network among several leading European groups in these research areas in order to accelerate the discovery process at a very expansive moment in the field that will finally lead to unraveling of the molecular mechanisms of neurological and endocrine diseases associated with the GDNF-RET system.
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 parkinson
- medical and health sciences basic medicine neurology amyotrophic lateral sclerosis
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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
00014 Helsinki
Finland
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