Objectif Neurodegenerative disorders, a heterogeneous group of chronic progressive diseases, are among the most puzzling and devastating diseases in medicine. Indeed they are characterized by onset in adult life, distinct clinical phenotypes, and specific degeneration of subsets of neurons and axons. Hereditary spastic paraplegia (HSP) is a disorder that results in progressive weakness and spasticity of the lower limbs affecting approximately 1 in 10000 individuals. Heterogeneity characterizes HSP in both clinical and genetic aspects. Little is known about the pathogenesis of HSP and consequently no specific treatment is available to prevent, cure or delay progression of symptoms of HSP. Electrophysiological and pathological findings point to the corticospinal, dorsal columns and spinocerebellar fibers as the structures primarily affected by HSP. Two main pathogenetic hypotheses for the neurodegeneration seen in HSP, as well as other neurodegenerative conditions, have recently emerged, suggesting that impaired mitochondrial function and/or defective subcellular transportation mechanics play a crucial role. In fact, HSP-causing mutations have been found in gene products involved in mitochondrial function, such as paraplegin and HSP60, and axonal trafficking, such as kinesin and, possibly, spastin and spartin. This consortium of European groups intends to provide a multi-faceted comprehensive approach to study pathogenesis of HSP with a particular emphasis on the role of mitochondrial dysfunction and impaired axonal transport, through the production and characterization of six novel mouse models for this disease, in parallel with the recently developed paraplegin null mutant. The proposed strategy is a highly integrated effort to study the function of several HSP genes, with the final goal of identifying common mechanisms leading to axonal degeneration, which will be potential targets of a therapeutic intervention in the long term. Champ scientifique natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingmedical and health sciencesbasic medicineneurologydementianatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineophthalmologyretinopathy Mots‑clés animal model hereditary spastic paraplegia motoneuron neurodegeneration Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Thème(s) LSH-2002-2.1.3-7 - Rare monogenic neurological disorders Appel à propositions FP6-2002-LIFESCIHEALTH Voir d’autres projets de cet appel Régime de financement STREP - Specific Targeted Research Project Coordinateur FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR Contribution de l’UE Aucune donnée Adresse Via Olgettina 60 MILANO Italie Voir sur la carte Coût total Aucune donnée Participants (5) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FONDAZIONE TELETHON Italie Contribution de l’UE Aucune donnée Adresse Via G. Sliceto 5 ROMA Voir sur la carte Coût total Aucune donnée AARHUS UNIVERSITET Danemark Contribution de l’UE Aucune donnée Adresse Nordre Ringgade 1 AARHUS C Voir sur la carte Coût total Aucune donnée UNIVERSITAET ZU KOELN Allemagne Contribution de l’UE Aucune donnée Adresse Albertus Magnus Platz KOELN Voir sur la carte Coût total Aucune donnée ST GEORGE'S HOSPITAL MEDICAL SCHOOL Royaume-Uni Contribution de l’UE Aucune donnée Adresse Cranmer Terrace LONDON Voir sur la carte Coût total Aucune donnée KLINIKUM DER FRIEDRICH-SCHILLER-UNIVERSITAET JENA Allemagne Contribution de l’UE Aucune donnée Adresse Bachstrasse 18 JENA Voir sur la carte Coût total Aucune donnée