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Neuronal death is a major contributor to many neural pathologies, including stroke, epilepsy, Parkinson's disease, Alzheimer's disease and many others. The adverse effects of neuronal death have an enormous economical and social impact. It is therefore urgent to understand the control mechanisms of neuronal death and to develop new tools for preventing it. A major project funded by the European Biotechnology program, is directed to these aims.
Sharing techniques, know-how and ideas we developed several new ways of preventing or delaying neuronal death in several situations, both in vivo and in vitro, and we gained considerable new understanding of the cellular mechanisms that bring about the cell death. In the project we:
- made substantial advances in understanding the roles of a family of cell death promoting genes known as caspases, and of two cell-protective genes called bcl-2 and superoxide dismutase;
- shown the death-promoting roles of the release of calcium and cytochrome C into the cytoplasm of dying neurons;
- have developed a variety of pharmacological strategies for preventing this cell death.
The project main deliverables are:
- New pharmacological blockers of neuronal death.
- Transgenic mice expressing neuron-survival genes.
- Mutant mice (reeler, lurcher) crossed with transgenics.
- A novel system for imaging living cells in explants.
- A system for neurotrophin release in vivo.
In the long term this should lead to new and more effective ways of preventing the neuronal death that occurs in neurodegenerative diseases and other neural pathologies.
Project Participants:
Dr. Jean-Claude Martinou (Serono, Geneva, Switzerland).
Dr. Peter G.H. Clarke (Universite' de Lausanne, Switzerland).
Dr. Lucia Galli-Resta (Neurofisiologia CNR, Pisa, Italy). coordinator
Dr. Jean Mariani (Universite P. & M. Curie, Paris, France).
Dr. Roberto Navarrete (Imperial College, London, U.K.).
Dr. Ian Thompson (University of Oxford, U.K.).
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