Neuro-degenerative diseases represent a major social and economic problem for the Community; they are characterised by the cell death of specific populations of neurons. No cures currently exist: good candidates would be drugs that inhibit intracellular signalling pathways involved in cell death, or stimulate signalling for survival, but we know little about how the pathways are regulated in neurons in normal or pathological situations. Our transnational project involving academic, clinical and industrial partners is aimed at a better understanding of the role of several novel mechanisms. We will study in neurons the control mechanisms and signalling pathways involved. We aim to generate important new data in this fast-moving field, and to define novel potential targets for drug discovery.
The project was successful in achieving the majority of its main objectives, and the continuous interaction between groups in a fast-moving field led to many results and publications (nealry 80 in international peer-reviewed journals) that could not have been predicted at the start of the project.
Our major findings were:
1. We discovered new intracellular signalling pathways that regulate neuronal death or survival. These may be useful targets for therapeutic intervention in patients;
2. We demonstrated unexpected roles for neurotrophic factors in development and functioning of the nervous system. These open new avenues of potential application for these factors and also inform of potential side effects;
3. We found that signalling pathways interact in complex manners to determine the development, survival or death of specific neuronal populations within the nervous system. This is likely to have repercussions for the design of neuroprotective strategies in patients;
4. We demonstrated that, in addition to external triggers, the death or survival of a given neuron is strongly regulated by intrinsic determinants. This may explain the selective loss of certain neurons in patients with neurodegenerative disease.
Call for proposalData not available
Funding SchemeCSC - Cost-sharing contracts
171 77 Stockholm
EH1 1HN Edinburgh