Dr. Cristina Fasolato works at the Department of Biomedical Sciences in the research group directed by Prof. Tullio Pozzan. In close collaboration with Dr. Paola Pizzo, she is now focusing her interest on the role played by Ca2+ dysregulation in Alzheimer's Disease.
Alzheimer's Disease (AD) is a devastating neurological disorder whose frequency is steadily increasing also due to the extended life expectance of the human population. Although the majority of AD cases are sporadic, a significant fraction of AD is inherited in a dominant pattern. Mutations of the ubiquitously expressed presenilins comprise the majority of the familial forms of AD (FAD). Although the pathogenesis of AD is still obscure, understanding of the molecular defects of FAD may help in clarifying the pathogenesis not only of the genetic but also of the sporadic AD. Our research is focused on the mechanisms through which presenilin mutations affect Ca2+ handling by intracellular organelles (endoplasmic reticulum, Golgi apparatus and mitochondria) and their link to neuronal degeneration as well as on the effects of amyloid-beta peptides on cellular Ca2+ handling. These issues are investigated by classical Ca2+ probes, recombinant aequorins and cameleons targeted to organelles and micro-environments in different model cells, primary neuronal cultures and brain slices from transgenic AD mouse models.
References:
1. L. Brunello, E. Zampese, C. Florean, T. Pozzan, P. Pizzo and C. Fasolato. Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake. (2009). Journal of Cellular and Molecular Medicine (in press) doi:10.1111/j.1582-4934.2009.00755.x
2. F. Facchinetti, C. Fasolato, E. Del Giudice, A. Burgo, S. Furegato, M. Fusco, E. Basso, R. Seraglia, A. D'Arrigo and A. Leon. Nimodipine selectively stimulates b-amyloid 1-42 secretion by a mechanism independent of calcium influx blockage (2006) Neurobiology of Aging 27, 218-227.
3. G. Zatti, A. Burgo, M. Giacomello, L. Barbiero, R. GhidoniI, G. Sinigaglia, C. Florean, S. Bagnoli, G. Binetti, S. Sorbi, P. Pizzo and C. Fasolato. Presenilin mutations linked to Familial Alzheimer's Disease reduce endoplasmic reticulum and Golgi apparatus calcium levels (2006). Cell Calcium 39, 539-550.
4. A. Burgo, G. Carmignoto, P. Pizzo, T. Pozzan and C. Fasolato. Paradoxical Ca2+ Rises Induced by Low External Ca2+ in Hippocampal Neurones. (2003) J. Physiol. 549.2, 537-552.