Objetivo Ageing is the main correlate of dementia and several other neurodegenerative diseases which currently affect more than 6 million people in Europe. Molecular understanding of these brain conditions is important for their prevention and treatment. In mice, pathological granular structures positive for periodic acid-Schiff stain have been found in the hippocampus with increasing age. The degenerative process of granule formation appears to originate in astrocytes, but adjacent neuronal structures are affected and, accordingly, associated memory impairments have been described. Recent studies reported that granules express glycosidic neo-epitopes, a hallmark of the degenerative granule formation process. This neo-epitope has additionally been found in Lafora bodies of a mouse model of Lafora disease, a fatal neurodegenerative condition. On the other hand, mice serum contains natural IgM antibodies that recognise the glycosidic neo-epitope, suggesting a potentional removal mechanism. In this project, I aim to describe the structure of the glycosidic neo-epitopes of the hippocampal granules as well as the composition of the degenerative granules and Lafora bodies. To achieve these goals, I will employ a multidisciplinary approach exploiting glycomics and neurobiology, with the application of leading-edge technologies that include histological methods, analytical techniques, MALDI-MS imaging and laser-capture microdissection. Moreover, the binding patterns of the anti-neo-epitope natural IgMs will also be explored. Finally and importantly, the expression of the glycosidic neo-epitope in human brain will be assessed. Overall, the knowledge generated will provide new data on brain degenerative processes underlying age-related memory impairments in humans. Ultimately this project will generate new insights for the use of glycosidic neoepitopes as biomarkers for ageing and neurodegenerative diseases, and for prevention and therapeutic strategies using natural antibodies. Ámbito científico natural sciencesbiological sciencesneurobiologymedical and health sciencesclinical medicinegerontologymedical and health sciencesbasic medicineneurology Palabras clave Ageing dementia neo-epitope glycoconjugate Periodic Acid Schiff Lafora bodies corpora amylacea natural antibodies hippocampus MALDI imaging laser capture microdissection biomarker Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2015 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinador THE UNIVERSITY OF LIVERPOOL Aportación neta de la UEn € 183 454,80 Dirección BROWNLOW HILL 765 FOUNDATION BUILDING L69 7ZX Liverpool Reino Unido Ver en el mapa Región North West (England) Merseyside Liverpool Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 183 454,80