Agnese Secondo
Agnese Secondo
affiliation: Università di Napoli Federico II
research area(s): Neuroscience, Experimental Medicine
  • Neurosciences
  • Molecular Pathology and Pathophysiology
University/Istitution: Università di Napoli Federico II
Agnese Secondo, born in Naples (Italy) on 1973, is Assistant Professor of Pharmacology since 2004 at the School of Medicine, "Federico II" University of Naples, Italy. In 1996 she got her degree in Chemistry and Pharmaceutical Technology (110/110) at School of Pharmacy, "Federico II" University of Naples, Italy. In 2001 she got her PhD in Neuropsicopharmacology and Toxicology at School of Medicine, "Federico II" University of Naples, Italy. In 2004 she got her Faculty in Pharmacology and Clinical Toxicology at School of Medicine, "Federico II" University of Naples, Italy. She keep relationships with several research groups in Italy and Europe. She worked in UK as Visiting Researcher in the neuroscience group directed by Pierluigi Nicotera at Medical Research Center (MRC) in Leicester. She is the author of 42 publications on international scientific journals and several chapters on Scientific books on contemporary Neuroscience. In 2006 she received the NicOX Young Researcher Award for the international pubblication: "Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents" Secondo et al. Am J Physiol cell physiol 2006; 290:C233-C243 (2006). His research is focused to the characterization of the ionic mechanisms involved in the pathogenesis of cellular damage that underlie neurodegenerative diseases. In particular, starting from the study of Ca2+ homeostasis in pathological conditions she is now studying the dysregulation of this homeostasis at the level of the endoplasmic reticulum and nuclear compartment. She has n° 2 international patent (prodrugs of L- e D-arginine; BDZ molecule with a neuroprotective profile). She is membership of the following scientific societies: Italian Society of Pharmacology and Italian Society of Neuroscience. She is referee of the following international journals J. Neurochem, Am. J. Physiology, Neuroscience, JPET, Molecular Pharmacology, Cell death and Differentiation, Cell Calcium.
Introduction: the relevance of Ca2+ ions in the neurodegenerative diseases has been recognized for about 3 decades. The "calcium overload hypothesis" indicates that Ca2+ cytotoxicity depend on intracellular Ca2+ concentration exceeding a given threshold. On the other hand, "source specificity hypothesis" reasons that Ca2+ toxicity occurs not simply as a function of increased Ca2+ concentration within the cytosol, but is instead linked to the route of Ca2+ and to the pathways activated. Very recently, the dysfunction of Ca2+ homeostasis within the endoplasmic reticulum (ER) has been indicated as a specific biochemical feature of the neurodegenerative process (Sirabella et al. 2009). ER is linked to the nuclear envelope that surrounded the nucleus, thus suggesting a functional relationship between the two organelles. On the other hand, plasma membrane is related to ER since the main calcium entry pathway activated after ER depletion is represented by the so called store-operated calcium channels (SOCs). Molecularly, the stromal interacting molecule (STIM1) and the Orai family represent the key components of SOC. At the present time, the relationship among the ER machinery- consisting on STIM1, ORAI1 and ER- and other organelles storing calcium such as nucleus and acidic stores still remains absolutely unknown. This occurs not only in physiological but also in pathological conditions including neurodegeneration. Objectives: To establish in the neurodegenerative diseases including stroke: 1. the role and the regulation of Ca2+ stores (i.e. ER, nucleus, acidic organelles); 2. the role of such proteins involved in Ca2+ handling including the three isoforms of the Na+-Ca2+ exchanger at the level of these Ca2+ stores; 3. the functional relationship among SOCs, nucleus and acidic stores. Methods: an integrated approach based on the use of in vivo and in vitro models mimicking stroke and other forms of neurodegeneration, conventional and confocal microscopy, single-cell microfluorimetry, electrophysiology, immunocytochemistry, molecular biology are usually adopted.
Formisano L, Guida N, Cocco S, Secondo A, Sirabella R, Ulianich L, Paturzo F, Di Renzo G, Canzoniero LM.(2011) The transcription factor REST is a novel molecular target for the neurotoxic effect of the polychlorinated biphenyl mixture Aroclor 1254 in neuroblastoma SH-SY5Y cells.J Pharmacol Exp Ther. 2011 Jun 21
Russo M, Cocco S, Secondo A, Adornetto A, Bassi A, Nunziata A, Polichetti G, De Felice B, Damiano S, Serù R, Mondola P, Di Renzo G. (2001)Cigarette smoke condensate causes a decrease of the gene expression of Cu-Zn superoxide dismutase, mn superoxide dismutase, glutathione peroxidase, catalase, and free radical-induced cell injury in SH-SY5Y human neuroblastoma cells.
Neurotox Res. 19:49-54.
Molinaro P, Viggiano D, Nisticò R, Sirabella R, Secondo A, Boscia F, Pannaccione A, Scorziello A, Mehdawy B, Sokolow S, Herchuelz A, Di Renzo GF, Annunziato L (2011) Na+-Ca2+ Exchanger (NCX3) Knock-Out Mice Display an Impairment in Hippocampal Long-Term Potentiation and Spatial Learning and Memory. J Neurosci 31:7312-7321
Secondo A, Molinaro P, Pannaccione A, Esposito A, Cantile M, Lippiello P, Sirabella R, Iwamoto T, Di Renzo G, Annunziato L (2011) Nitric oxide stimulates NCX1 and NCX2 but inhibits NCX3 isoform by three distinct molecular determinants. Mol Pharmacol 79:558-68
Berni Canani R, Secondo A, Passariello A, Buccigrossi V, Canzoniero LM, Ruotolo S, Puzone C, Porcaro F, Pensa M, Braucci A, Pedata M, Annunziato L, Guarino A.(2010)Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes.Eur J Pharmacol.626:266-70.
Staiano RI, Granata F, Secondo A, Petraroli A, Loffredo S, Frattini A, Annunziato L, Marone G, Triggiani M.(2009)Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes.Eur J Immunol. 39:1405-18.
Luisi R, Panza E, Barrese V, Iannotti FA, Viggiano D, Secondo A, Canzoniero LM, Martire M, Annunziato L, Taglialatela M.(2009)Activation of pre-synaptic M-type K+ channels inhibits [3H]D-aspartate release by reducing Ca2+ entry through P/Q-type voltage-gated Ca2+ channels.J Neurochem.109:168-81.
Secondo A, De Mizio M, Zirpoli L, Santillo M, Mondola P. (2008) The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells.Biochem Biophys Res Commun. 376:143-7.
Boscia F, Gala R, Pannaccione A, Secondo A, Scorziello A, Di Renzo G, Annunziato L (2009) NCX1 expression and functional activity increase in microglia invading the infarct core. Stroke 40:3608-17
Secondo A, Pannaccione A, Molinaro P, Ambrosino P, Lippiello P, Esposito A, Cantile M, Khatri PR, Melisi D, Di Renzo G, Annunziato L (2009) Molecular pharmacology of the amiloride analog 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-n-[[(2,4-dimethylbenzyl)-amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) as a pan inhibitor of the Na+-Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in stably transfected cells. J Pharmacol Exp Ther 331:212-21
Sirabella R, Secondo A, Pannaccione A, Scorziello A, Valsecchi V, Adornetto A, Bilo L, Di Renzo G, Annunziato L (2009) Anoxia-induced NF-kappaB-dependent upregulation of NCX1 contributes to Ca2+ refilling into endoplasmic reticulum in cortical neurons. Stroke 40:922-9
Molinaro P, Cuomo O, Pignataro G, Boscia F, Sirabella R, Pannaccione A, Secondo A, Scorziello A, Adornetto A, Gala R, Viggiano D, Sokolow S, Herchuelz A, Schurmans S, Di Renzo G, Annunziato L (2008) "Target distruption of Na+-Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage". J Neurosc 28:1179-1184
Cuomo O, Gala R, Pignataro G, Boscia F, Secondo A, Scorziello A, Pannaccione A, Viggiano D, Adornetto A, Molinaro P, Li XF, Lytton J, Di Renzo G, Annunziato L (2008) "A critical role for the potassium-dependent sodium-calcium exchanger NCKX2 in protection against focal ischemic brain damage". J Neurosc 28:2053-63
Molinaro P, Cuomo O, Pignataro G, Boscia F, Sirabella R, Pannaccione A, Secondo A, Scorziello A, Adornetto A, Gala R, Viggiano D, Sokolow S, Herchuelz A, Schurmans S, Di Renzo G, Annunziato L (2008) "Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage". J Neurosc 28:1179-1184
Formisano L, Saggese M, Secondo A, Sirabella R, Vito P, Valsecchi V, Molinaro P, Di Renzo G, Annunziato L (2008) "The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway". Mol Pharm 73:727-37
Project Title:
Study on the molecular mechanism of the amino acid L-BMAA in experimental models of ALS and Parkinson Disease
In amyotrophic Lateral Sclerosis (ALS) the motor neurons of the ventral horn of the spinal cord and the pyramidal neurons of motor cortex are compromised . Three classifications of ALS have been described: the sporadic form that comprises 90 to 95% of all cases, the familial form (fALS) accounting for 5 to 10% of all cases, and, finally, the Guamanian form with an high incidence in Guam and the Trust Territories of the Pacific. The cause of the motor neuron loss in ALS is unknown, but theories include excitotoxicity, free-radical toxicity, abnormal protein aggregation and viral infection and autoimmunity. Excitotoxins including glutamate, AMPA (alpha-amino-hydroxy-5-methylisoxasole-4 propionic acid) and kainate togheter with the amino acid L-BMAA are thought to induce neuronal death by triggering free-radical production into motor neurons, thus stimulating an intraneuronal cascade mechanism that ultimately results in neuronal death. The presence of chromosome 21 superoxide dismutase 1 (SOD1) gene mutation (G93A) is present in some families with a history of familial ALS. SOD1 has an important role in the metabolism of potentially neurotoxic free radicals. Animals transgenic for the mutant SOD do develop progressive motor neuron disease. Nevertheless, despite intense research, the putative role played by mutant SOD1 and the mechanism of L-BMAA remain elusive. Methods: determination of intracellular calcium levels both in the cytoplasm and in organelles such as endoplasmic reticulum and mitochondria in primary neurons treated with L-BMAA or dissected from G93A mice brain by means of single-cell microfluorimetry.