Objective The description of the initial molecular events in Huntington's disease is crucial to design therapeutic intervention for the cure of this devastating disorder. In this proposal, I plan to identify the early HD-trigger mechanism, aiming for the development of rational therapeutics. Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder due to an expanded, unstable CAG repeated sequence that elongates a segment of glutamine residues in the HD gene's protein product, huntingtin.The disease is characterized by progressively worsening chorea, psychiatric impairment and cognitive decline. The most striking pathological manifestation of HD is a specific and gradual loss of neurons, predominantly in the caudate nucleus and putamen of the brain. I propose, via a combinatorial screening, to isolate small peptides that specifically bind mutant huntingtin and that are able to reverse in vivo pathogenic phenotypes by displacing crucial protein-protein interactions.An aptamer with such characteristics will represent a very exciting lead to design small drugs for therapeutic intervention. I anticipate that this study will provide a better understanding of the first molecular events of the disease, providing suitable targets for therapeutic intervention. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinecardiologycardiovascular diseases Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Call for proposal FP6-2002-MOBILITY-12 See other projects for this call Funding Scheme IRG - Marie Curie actions-International re-integration grants Coordinator INTERNATIONAL SCHOOL FOR ADVANCED STUDIES EU contribution No data Address Via Beirut 2-4 TRIESTE Italy See on map Links Website Opens in new window Total cost No data