Objetivo The worldwide aging population will lead to a dramatic increase in the number of people with Alzheimer’s disease and other incurable age-related neurodegenerative diseases over the next few decades. By 2050 over 115 million are expected to suffer from these devastating diseases. The major pathological hallmark of these disorders is the accumulation of aggregation-prone disease proteins in aggregates in the brain. To understand the disease mechanisms and to identify targets for treatment, I aim to uncover the cellular pathways that regulate disease-protein toxicity and aggregation (proteotoxicity).Opening up such exciting new avenues for research is our recent identification of a modifier of aggregation, which we named MOAG-4, as a general regulator of age-related proteotoxicity in worm (C. elegans) models for neurodegenerative diseases. MOAG-4 and its human counterpart SERF act independently of classical pathways that degrade proteins or prevent their aggregation, but their molecular role remains to be determined. I hypothesize that MOAG-4/SERF represents a new regulatory pathway of age-related proteotoxicity in neurodegenerative diseases.With an ERC starting grant, I will uncover the pathway in which MOAG-4/SERF is operating, establish the mechanism by which the pathway regulates proteotoxicity, establish the evolutionarily conservation of the pathway in human cells, and establish its potential as a therapeutic target in patient-derived cells. By combining the power of C. elegans genetics with the development of cell-biological tools to visualize and monitor aggregation and toxicity in living and aging worms and in patient-derived cells, we will be at the forefront of providing new insights into disease-mechanisms. Our discoveries will offer new starting points for research and for the development of therapeutic interventions in the early molecular events of aging-associated neurodegenerative diseases. Ámbito científico natural sciencesbiological sciencesgeneticsmedical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2011-StG_20101109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida ACADEMISCH ZIEKENHUIS GRONINGEN Aportación de la UE € 1 450 249,00 Dirección HANZEPLEIN 1 9713 GZ Groningen Países Bajos Ver en el mapa Región Noord-Nederland Groningen Overig Groningen Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Henk Heidekamp (Dr.) Investigador principal Ellen Nollen (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo ACADEMISCH ZIEKENHUIS GRONINGEN Países Bajos Aportación de la UE € 1 450 249,00 Dirección HANZEPLEIN 1 9713 GZ Groningen Ver en el mapa Región Noord-Nederland Groningen Overig Groningen Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Henk Heidekamp (Dr.) Investigador principal Ellen Nollen (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos