Obiettivo 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. Campo scientifico natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingmedical and health sciencesbasic medicineneurologydementianatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineophthalmologyretinopathy Parole chiave animal model hereditary spastic paraplegia motoneuron neurodegeneration Programma(i) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Argomento(i) LSH-2002-2.1.3-7 - Rare monogenic neurological disorders Invito a presentare proposte FP6-2002-LIFESCIHEALTH Vedi altri progetti per questo bando Meccanismo di finanziamento STREP - Specific Targeted Research Project Coordinatore FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR Contributo UE Nessun dato Indirizzo Via Olgettina 60 MILANO Italia Mostra sulla mappa Costo totale Nessun dato Partecipanti (5) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto FONDAZIONE TELETHON Italia Contributo UE Nessun dato Indirizzo Via G. Sliceto 5 ROMA Mostra sulla mappa Costo totale Nessun dato AARHUS UNIVERSITET Danimarca Contributo UE Nessun dato Indirizzo Nordre Ringgade 1 AARHUS C Mostra sulla mappa Costo totale Nessun dato UNIVERSITAET ZU KOELN Germania Contributo UE Nessun dato Indirizzo Albertus Magnus Platz KOELN Mostra sulla mappa Costo totale Nessun dato ST GEORGE'S HOSPITAL MEDICAL SCHOOL Regno Unito Contributo UE Nessun dato Indirizzo Cranmer Terrace LONDON Mostra sulla mappa Costo totale Nessun dato KLINIKUM DER FRIEDRICH-SCHILLER-UNIVERSITAET JENA Germania Contributo UE Nessun dato Indirizzo Bachstrasse 18 JENA Mostra sulla mappa Costo totale Nessun dato