Paola Pizzo

Qualifica: Ricercatore Universitario confermato
SSD: MED04 Facoltà: Medicina e Chirurgia
Gruppo di ricerca: Second messenger homeostasis in subcellular compartments
Telefono: +39 049 827 6067
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Studio: secondo piano nord, stanza 58

Attività didattica

• Corso di Laurea Specialistica in Medicina e Chirurgia, Corso Integrato di Patologia Generale e Fisiopatologia, MED 1. Citopatologia
• Corso di Laurea Triennale in Terapia della Neuro e Psicomotricità dell’Età Evolutiva, Corso Integrato di Fisiologia, Patologia Generale e Neuropsichiatria Infantile, Patologia Generale

Ricevimento studenti: su appuntamento per email

Main research interest:
The main scientific interest is the control of Ca²⁺ homeostasis in living cells. Within this framework, a major theme of the research is testing the “Ca²⁺ hypothesis” for Alzheimer’s Disease pathogenesis.

New insights into Alzheimer’s Disease Ca²⁺ dysregulation by organelle-targeted fluorescent probes
Evidence has accumulated showing that Familial Alzheimer's Disease (FAD) is linked to an imbalance of cellular Ca²⁺ homeostasis. Presenilins (PSs), the catalytic core of -secretase, the enzyme responsible of -amyloid (A production, play a key role in the control of Ca²⁺ leak out of the endoplasmic reticulum (ER). We have demonstrated that PS2, but not PS1, mutants consistently lower ER and Golgi Ca²⁺ levels by a mechanism that primarily relies on SERCA pump inhibition and, secondarily on increased leakage through the Ca²⁺ release channels IP3Rs and RyRs. Our hypothesis is that FAD-PS2 mutations decrease, instead of increasing, the store Ca²⁺ content, partially contrasting the damaging effect of an augmented A production, due to mutated PSs. We are now developing and applying new FRET-based Ca²⁺ probes (cameleons) to monitor Ca²⁺ concentration at the level of single cell microdomains, such as ER, mitochondria, trans-Golgi apparatus, plasma membrane sub-domains and peroxisomes in neurons and astrocytes from AD mouse models.

Primary brain cells from transgenic AD mice expressing the new FRET-based Ca2+ probes (cameleons) targeted either to ER (green) or mitochondria (red)

Selected publications:

1. Zampese E., Brunello L., Fasolato C. and Pizzo P. (2009). Ca²⁺ dysregulation mediated by presenilins in Familial Alzheimer’s Disease: causing or modulating factor? Current Trends in Neurology, in press
2. Brunello L., Zampese E., Florean C., Pozzan T., Pizzo P. and Fasolato C. (2009) Presenilin-2 dampens intracellular Ca²⁺ stores by increasing Ca²⁺ leakage and reducing Ca²⁺ uptake. J Cell Mol Med. 2009 Mar 27. PMID: 19382908.
3. Florean C., Zampese E., Zanese M., Brunello L., Ichas F., De Giorgi F. and Pizzo P. (2008) High content analysis of -secretase activity reveals variable dominance of presenilin mutations linked to familial Alzheimer's disease. BBA - Molecular Cell Research, 1783:1551-60.
4. Drago I, Giacomello M, Pizzo P, Pozzan T. (2008) Calcium dynamics in the peroxisomal lumen of living cells. J Biol Chem. 283:14384-90
5. Pizzo P. and Pozzan T. (2007) Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics. Trends Cell Biol., 17, 511-517.
6. Zatti G., Burgo A., Giacomello M., Barbiero L., Guidoni R., Sinigaglia G., Florean C., Bagnoli S., Binetti G., Sorbi S., Pizzo P. and Fasolato C. (2006) Presenilin mutations linked to Familial Alzheimer’s Disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium, 39, 539-550.
7. Giacomello M., Barbiero L., Zatti G., Squitti R., Binetti G., Pozzan T., Fasolato C., Ghidoni R. and Pizzo P. (2005). Reduction of Ca²⁺ stores and Capacitative Ca²⁺ Entry is associated with the Familial Alzheimer’s Disease presenilin-2 T122R mutation and anticipates the onset of dementia. Neurobiology of Disease, 18, 638-648.
8. Zatti G., Ghidoni R., Barbiero L., Binetti G., Pozzan T., Fasolato C., and Pizzo P. (2004) The presenilin 2 M239I mutation associated with familial Alzheimer disease reduces Ca²⁺ release from intracellular stores. Neurobiology of Disease, 15, 269-278.