Objective
Programmed cell death/apoptosis plays an important role during brain development and controls the accurate number of neurons surviving to adulthood. This process of natural cell death is regulated by neurotrophic factors present in the target tissue or in their close environment. However, there are some recent evidence fo the involvement of apoptosis in neurodegenerative disorders and in other forms of neurological diseases. The results of many studies have now established the existence of specific intracellular protein which either promote or inhibit apoptosis in different systems. To the former classes of pro-apoptotic proteins belong, among others, p53, BAX and the various cysteine proteases (Caspases), whilst the antiapoptotic protein family consists of Bc1-2, with its related family members, of the newly cloned tmammalian inhibitor of apoptosis proteins (IAPs), and of the defender against apoptosis protein (DAD). Although our knowledge of Caspases and the Bc1-2 classes of proteins has increased steadily, less is know about the role of the various IAPs and DAD in brain tissue or about their mechanism of action However as shown for one of the IAP proteins, NAIP, the protein is involved in the spinal muscular atrophy disease (SMA) which is an autosomal recessive disease affecting children. The work proposed here aims to increase our knowledge about IAP,DAD in developing and injured brain, and to study their regulation by neurotrophic factors. The important question of their interaction with both known(Caspases and Bc1-2) and unknown proteins, determining neuronal survival will also be pursued. These questions will be analysed using a wide range of methods of molecular- and cell biology, biochemistry as well as in vivo studies or ischemic brain and on cerebellar mutants. In an attempt to understand the structural-functional relationships of the IAPs crystallisation of the proteins (NAIP) XIAP) will be undertaken. Finally, transgenic techniques and targeted gene disruption will help to elucidate the particular function of the various gene products in vivo.
It is to be expected that the results of these studies on proteins involved in neuronal apoptosis will help us to understand better the complex mechanism by which nerve cell survival is regulated. In view of involvement of apoptosis in brain disease the study may also learn us how to counteract cell death and neurodegeneration. As described in more detail in the work content, the work proposed is multidisiplinary in nature, it addresses basic mechanisms of brain development at the molecular level and represents a collaboration between five labs in different countries. Each team contributes its own skill and expertise and it is also clear that the work could not be carried out by a single group alone.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencescell biology
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Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
751 23 Uppsala
Sweden