Pasquale Molinaro
e-mail: pasquale.molinaro AT unina.it
website: www.unina.it
affiliation: Università di Napoli Federico II
research area(s): Neuroscience
Courses:
- Genetics and Molecular Medicine
- Neurosciences
Date of birthOctober 14th, 1979
Place of birth Caserta (ITALY)
Professional addressDivision of Pharmacology, Department of Neuroscience, Reproductive and OdontostomatologicSciences, School of Medicine, “Federico II” University of Naples, Naples (ITALY)
Education
2003 PharmaceuticalBiotechnologiesdegree, 110/110, “Federico II” University of Naples, Italy.
2008 PhDdegree in Neuroscience, School of Medicine, “Federico II” University of Naples, Italy.
2012- Assistant Professor in Pharmacology, School of Medicine, “Federico II” University of Naples, Italy.
ResearchSupport
Futuro in Ricerca 2013, MIUR (ITALY)
Place of birth Caserta (ITALY)
Professional addressDivision of Pharmacology, Department of Neuroscience, Reproductive and OdontostomatologicSciences, School of Medicine, “Federico II” University of Naples, Naples (ITALY)
Education
2003 PharmaceuticalBiotechnologiesdegree, 110/110, “Federico II” University of Naples, Italy.
2008 PhDdegree in Neuroscience, School of Medicine, “Federico II” University of Naples, Italy.
2012- Assistant Professor in Pharmacology, School of Medicine, “Federico II” University of Naples, Italy.
ResearchSupport
Futuro in Ricerca 2013, MIUR (ITALY)
The research of Dr. Molinaroisaimed to study the new compoundsthatmodulates the learning and memoryprocesses and neuronaldamageinduced by ischemia, with particularregard to the role of proteinsable to modulate the homeostasis of sodium and calciumions. Thesestudieswereconductedusingseveralmolecularbiologytechniques (DNA cloning, in vitro transcription, reverse transcription of RNA, Real-Time PCR, Western blot, genotyping, stabletransfection, mutagenesis) and geneticmodifiedanimals
NCX3 regulatesmitochondrialcalciumhandlingthrough AKAP121-anchored signalingcomplex and preventshypoxia-inducedcelldeath.Scorziello A, Savoia C, Sisalli MJ, Adornetto A, Secondo A, Boscia F, Esposito A, Polishchuk EV, Polishchuk RS, Molinaro P, Carlucci A, Lignitto L, Di Renzo G, Feliciello A, Annunziato L.J Cell Sci. 2013 Oct 7.
Geneticallymodified mice as a strategy to unravel the roleplayed by the Na(+)/Ca (2+) exchanger in brain ischemia and in spatiallearning and memorydeficits.Molinaro P, Cataldi M, Cuomo O, Viggiano D, Pignataro G, Sirabella R, Secondo A, Boscia F, Pannaccione A, Scorziello A, Sokolow S, Herchuelz A, Di Renzo G, Annunziato L.AdvExpMedBiol. 2013
New insights in mitochondrialcalciumhandling by sodium/calciumexchanger.Scorziello A, Savoia C, Secondo A, Boscia F, Sisalli MJ, Esposito A, Carlucci A, Molinaro P, Lignitto L, Di Renzo G, Feliciello A, Annunziato L.AdvExpMedBiol. 2013
NCX1 is a new rest target gene: role in cerebral ischemia.Formisano L, Guida N, Valsecchi V, Pignataro G, Vinciguerra A, Pannaccione A, Secondo A, Boscia F, Molinaro P, Sisalli MJ, Sirabella R, Casamassa A, Canzoniero LM, Di Renzo G, Annunziato L.NeurobiolDis. 2013
Neurounina-1, a novel compound thatincreases Na+/Ca2+ exchangeractivity, effectivelyprotectsagainststrokedamage.Molinaro P, Cantile M, Cuomo O, Secondo A, Pannaccione A, Ambrosino P, Pignataro G, Fiorino F, Severino B, Gatta E, Sisalli MJ, Milanese M, Scorziello A, Bonanno G, Robello M, Santagada V, Caliendo G, Di Renzo G, Annunziato L.MolPharmacol. 2013
A new concept: Aβ1-42 generates a hyperfunctionalproteolytic NCX3 fragmentthatdelays caspase-12 activation and neuronaldeath.Pannaccione A, Secondo A, Molinaro P, D'Avanzo C, Cantile M, Esposito A, Boscia F, Scorziello A, Sirabella R, Sokolow S, Herchuelz A, Di Renzo G, Annunziato L.J Neurosci. 2012
ERK1/2, p38, and JNK regulate the expression and the activity of the threeisoforms of the Na+ /Ca2+ exchanger, NCX1, NCX2, and NCX3, in neuronal PC12 cells.Sirabella R, Secondo A, Pannaccione A, Molinaro P, Formisano L, Guida N, Di Renzo G, Annunziato L, Cataldi M.J Neurochem. 2012
Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-termpotentiation and spatiallearning and memory.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.
J Neurosci. 2011
Nitricoxidestimulates NCX1 and NCX2 butinhibits NCX3 isoform by threedistinctmoleculardeterminants.
Secondo A, Molinaro P, Pannaccione A, Esposito A, Cantile M, Lippiello P, Sirabella R, Iwamoto T, Di Renzo G, Annunziato L.MolPharmacol. 2011
Molecularpharmacology of the amilorideanalog 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+ exchangerisoforms NCX1, NCX2, and NCX3 in stablytransfectedcells. Secondo A, Pannaccione A, Molinaro P, Ambrosino P, Lippiello P, Esposito A, Cantile M, Khatri PR, Melisi D, Di Renzo G, Annunziato L.
J PharmacolExpTher. 2009
A criticalrole for the potassium-dependentsodium-calciumexchanger NCKX2 in protectionagainstfocalischemic brain damage.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.J Neurosci. 2008
Targeteddisruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage.
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.J Neurosci. 2008
Geneticallymodified mice as a strategy to unravel the roleplayed by the Na(+)/Ca (2+) exchanger in brain ischemia and in spatiallearning and memorydeficits.Molinaro P, Cataldi M, Cuomo O, Viggiano D, Pignataro G, Sirabella R, Secondo A, Boscia F, Pannaccione A, Scorziello A, Sokolow S, Herchuelz A, Di Renzo G, Annunziato L.AdvExpMedBiol. 2013
New insights in mitochondrialcalciumhandling by sodium/calciumexchanger.Scorziello A, Savoia C, Secondo A, Boscia F, Sisalli MJ, Esposito A, Carlucci A, Molinaro P, Lignitto L, Di Renzo G, Feliciello A, Annunziato L.AdvExpMedBiol. 2013
NCX1 is a new rest target gene: role in cerebral ischemia.Formisano L, Guida N, Valsecchi V, Pignataro G, Vinciguerra A, Pannaccione A, Secondo A, Boscia F, Molinaro P, Sisalli MJ, Sirabella R, Casamassa A, Canzoniero LM, Di Renzo G, Annunziato L.NeurobiolDis. 2013
Neurounina-1, a novel compound thatincreases Na+/Ca2+ exchangeractivity, effectivelyprotectsagainststrokedamage.Molinaro P, Cantile M, Cuomo O, Secondo A, Pannaccione A, Ambrosino P, Pignataro G, Fiorino F, Severino B, Gatta E, Sisalli MJ, Milanese M, Scorziello A, Bonanno G, Robello M, Santagada V, Caliendo G, Di Renzo G, Annunziato L.MolPharmacol. 2013
A new concept: Aβ1-42 generates a hyperfunctionalproteolytic NCX3 fragmentthatdelays caspase-12 activation and neuronaldeath.Pannaccione A, Secondo A, Molinaro P, D'Avanzo C, Cantile M, Esposito A, Boscia F, Scorziello A, Sirabella R, Sokolow S, Herchuelz A, Di Renzo G, Annunziato L.J Neurosci. 2012
ERK1/2, p38, and JNK regulate the expression and the activity of the threeisoforms of the Na+ /Ca2+ exchanger, NCX1, NCX2, and NCX3, in neuronal PC12 cells.Sirabella R, Secondo A, Pannaccione A, Molinaro P, Formisano L, Guida N, Di Renzo G, Annunziato L, Cataldi M.J Neurochem. 2012
Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-termpotentiation and spatiallearning and memory.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.
J Neurosci. 2011
Nitricoxidestimulates NCX1 and NCX2 butinhibits NCX3 isoform by threedistinctmoleculardeterminants.
Secondo A, Molinaro P, Pannaccione A, Esposito A, Cantile M, Lippiello P, Sirabella R, Iwamoto T, Di Renzo G, Annunziato L.MolPharmacol. 2011
Molecularpharmacology of the amilorideanalog 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+ exchangerisoforms NCX1, NCX2, and NCX3 in stablytransfectedcells. Secondo A, Pannaccione A, Molinaro P, Ambrosino P, Lippiello P, Esposito A, Cantile M, Khatri PR, Melisi D, Di Renzo G, Annunziato L.
J PharmacolExpTher. 2009
A criticalrole for the potassium-dependentsodium-calciumexchanger NCKX2 in protectionagainstfocalischemic brain damage.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.J Neurosci. 2008
Targeteddisruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage.
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.J Neurosci. 2008
Project Title:
Project Title:
Characterization of the role played by NCX1 in learning and memory by using tissue-specific genetic modified animals
Three genes encoding for the Na+/Ca2+ exchanger family are expressed in CNS, named NCX1, NCX2 and NCX3. Recently, it has been demonstrated that NCX2 and NCX3 isoforms participate in hippocampal-dependent learning and memory processes by regulating the ionic homeostasis of Na+ and Ca2+.
It is conceivable that NCX1 could play a role in the mechanisms of hippocampal-dependent learning and memory since in the CNS this isoform is localized on both the synaptic boutons and neuronal body, where it influences synaptic vesicles recycling and cytosolic Ca2+ homeostasis during and after nerve terminal stimulation. Thus, the neuronal knock-out of NCX1 may increase the release of neurotransmitters at the presynaptic level and reduce cytosolic Ca2+ clearance at the post-synaptic level. In hippocampal neurons, this ionic derangement may lead to a fast and prolonged increase in cytosolic Ca2+ levels, which in turn may alter the synaptic plasticity and the mechanisms underlying hippocampal-dependent learning and memory processes as it occurs in ncx2-/- and ncx3-/- mice. However, the study of the relationship between NCX1 activity and the synaptic plasticity is hampered by the lack of selective drugs and by the death of ncx1-/- embryos due to heart disease. In this project, two conditioned and tissue-specific genetically modified mouse strains for NCX1 will be used in behavioural tests to evaluate the role played by NCX1 in hippocampal-dependent learning and memory processes.
It is conceivable that NCX1 could play a role in the mechanisms of hippocampal-dependent learning and memory since in the CNS this isoform is localized on both the synaptic boutons and neuronal body, where it influences synaptic vesicles recycling and cytosolic Ca2+ homeostasis during and after nerve terminal stimulation. Thus, the neuronal knock-out of NCX1 may increase the release of neurotransmitters at the presynaptic level and reduce cytosolic Ca2+ clearance at the post-synaptic level. In hippocampal neurons, this ionic derangement may lead to a fast and prolonged increase in cytosolic Ca2+ levels, which in turn may alter the synaptic plasticity and the mechanisms underlying hippocampal-dependent learning and memory processes as it occurs in ncx2-/- and ncx3-/- mice. However, the study of the relationship between NCX1 activity and the synaptic plasticity is hampered by the lack of selective drugs and by the death of ncx1-/- embryos due to heart disease. In this project, two conditioned and tissue-specific genetically modified mouse strains for NCX1 will be used in behavioural tests to evaluate the role played by NCX1 in hippocampal-dependent learning and memory processes.
Project Title:
Development of drugs selectively activating or inhibiting Na+/Ca2+ exchanger isoforms to ameliorate learning and memory deficits
Background:
Three genes encoding for the Na+/Ca2+ exchanger family are expressed in CNS, named NCX1, NCX2 and NCX3. Recently, it has been demonstrated that NCX2 and NCX3 isoforms participate in hippocampal-dependent learning and memory processes by regulating the ionic homeostasis of Na+ and Ca2+.
We will synthesize and characterize new compounds targeting NCX2 or NCX3 proteins starting from neurounina-1, designed and published by our research group as an NCX1 and NCX2 activator. In this project, we will test the effect of each drug on the activity of each NCX isoform in cellular lines stably transfected with NCX1, NCX2 or NCX3 to identify those compounds having high potency and selectivity for the single isoforms. The new drugs that selectively increase or inhibit NCX activity will then be tested for their effect on synaptic plasticity, using LTP and LTD as in vitro models, and hippocampal-dependent learning and memory performance in wild-type mice looking for the drugs that ameliorate learning and memory deficits.
Three genes encoding for the Na+/Ca2+ exchanger family are expressed in CNS, named NCX1, NCX2 and NCX3. Recently, it has been demonstrated that NCX2 and NCX3 isoforms participate in hippocampal-dependent learning and memory processes by regulating the ionic homeostasis of Na+ and Ca2+.
We will synthesize and characterize new compounds targeting NCX2 or NCX3 proteins starting from neurounina-1, designed and published by our research group as an NCX1 and NCX2 activator. In this project, we will test the effect of each drug on the activity of each NCX isoform in cellular lines stably transfected with NCX1, NCX2 or NCX3 to identify those compounds having high potency and selectivity for the single isoforms. The new drugs that selectively increase or inhibit NCX activity will then be tested for their effect on synaptic plasticity, using LTP and LTD as in vitro models, and hippocampal-dependent learning and memory performance in wild-type mice looking for the drugs that ameliorate learning and memory deficits.