Antonella Scorziello
e-mail: scorziel AT unina.it
website: www.unina.it
affiliation: Università di Napoli Federico II
research area(s): Neuroscience
Course:
Neurosciences
University/Istitution: Università di Napoli Federico II
University/Istitution: Università di Napoli Federico II
Antonella Scorziello was born in Naples on May 23 1966. She is graduated in Medicine (June 1990), Specialist in Pharmacology (October 1997), PhD in Neurophsycopharmacology and Toxicology (May 1997). She is Associate Professor of Pharmacology, Department of Neuroscience, Unit of Pharmacology, University of Naples Federico II (September 2010)
She is author of 51 papers published in international research Journals in the field of Neuroscience .
TRAINING IN FOREIGN LABORATORIES July-October 1990: Department of Internal Medicine University of Virginia, USA (Dr. D. Leong). June-October 2004 Mitochondrial Biology Group, Dipartimento di Fisiologia, University College of London (Prof. Michael Duchen). She is member of the following
SCIENTIFIC SOCIETY: Italian Society of Pharmacology,
Italian Society of Neuroscience, American Society for Neuroscience, Italian Society for Brain Aging
COLLABORATIONS WITH FOREIGN LABORATORY:
Prof. Michael Duchen, Mitochondrial Biology Group, Department of Physiology, University College of London UK
RESEARCH LINES
1. Characterization of the molecular mechanisms responsible for neuronal damage during anoxia and reoxygenation.
2. Characterization of the role of mitochondria in the induction of cellular damage in in vitro models of cerebral ischemia
3. Role of PKA and src in the regulation of mitochondrial calcium concentration in cellular models of hypoxia/reoxygenation
She is author of 51 papers published in international research Journals in the field of Neuroscience .
TRAINING IN FOREIGN LABORATORIES July-October 1990: Department of Internal Medicine University of Virginia, USA (Dr. D. Leong). June-October 2004 Mitochondrial Biology Group, Dipartimento di Fisiologia, University College of London (Prof. Michael Duchen). She is member of the following
SCIENTIFIC SOCIETY: Italian Society of Pharmacology,
Italian Society of Neuroscience, American Society for Neuroscience, Italian Society for Brain Aging
COLLABORATIONS WITH FOREIGN LABORATORY:
Prof. Michael Duchen, Mitochondrial Biology Group, Department of Physiology, University College of London UK
RESEARCH LINES
1. Characterization of the molecular mechanisms responsible for neuronal damage during anoxia and reoxygenation.
2. Characterization of the role of mitochondria in the induction of cellular damage in in vitro models of cerebral ischemia
3. Role of PKA and src in the regulation of mitochondrial calcium concentration in cellular models of hypoxia/reoxygenation
1. Characterization of the molecular mechanisms responsible for neuronal damage during anoxia and reoxygenation.
2. Characterization of the role of mitochondria in the induction of cellular damage in in vitro models of cerebral ischemia
3. Role of PKA and src in the regulation of mitochondrial calcium concentration in cellular models of hypoxia/reoxygenation
Mitochondrial biogenesis is an extremely complex process which involve the coordinated expression of mitochondrial and nuclear genes as well as the transport of nuclear gene products into mitochondria. Although the mechanisms involved in this process have been object of intensive studies during the last 20 years, the detailed mechanisms of the process are not yet completely clarified. What is known is that calcium ions are necessary to activate protein kinases able to recruit transcriptional factors and co-activators which in turn promote genes transcription and the expression of mitochondrial proteins. Moreover, this phenomenon is also associated to changes in mitochondrial morphology known as mitochondrial fission and fusion. The balance between these events is essential to the right mitochondrial function, and an impairment in the mechanisms involved in mitochondrial biogenesis might be involved in the pathogenesis of many neurodegenerative disease.
Objectives: the aim of this research line will be to investigate the mechanisms involved in mitochondrial biogenesis during ischemia/reperfusion with particular regard to the evaluation of:
(1) the changes in mitochondrial fission and fusion; (2) the changes in the expression of protein members of mitochondrial electron transport chain (ETC); (3) the role played by AKAP 121 and mitochondrial Na+/Ca2+ exchanger (NCX3) in the regulation of mitochondrial biogenesis.
Methods: The experiments of the present research line are performed in primary cultures of cortical neurons exposed to OGD. Confocal microscopy is used to assess mitochondrial morphology (fission and fusion) and to detect changes in mitochondrial membrane potential and calcium concentration. The activity of proteins member of the mitochondrial electron transport is evaluated by Blu Native Polyacrylamide Gel Electrophoresys (BN PAGE). Western Blotting analysis is used to evaluate protein expression.
2. Characterization of the role of mitochondria in the induction of cellular damage in in vitro models of cerebral ischemia
3. Role of PKA and src in the regulation of mitochondrial calcium concentration in cellular models of hypoxia/reoxygenation
Mitochondrial biogenesis is an extremely complex process which involve the coordinated expression of mitochondrial and nuclear genes as well as the transport of nuclear gene products into mitochondria. Although the mechanisms involved in this process have been object of intensive studies during the last 20 years, the detailed mechanisms of the process are not yet completely clarified. What is known is that calcium ions are necessary to activate protein kinases able to recruit transcriptional factors and co-activators which in turn promote genes transcription and the expression of mitochondrial proteins. Moreover, this phenomenon is also associated to changes in mitochondrial morphology known as mitochondrial fission and fusion. The balance between these events is essential to the right mitochondrial function, and an impairment in the mechanisms involved in mitochondrial biogenesis might be involved in the pathogenesis of many neurodegenerative disease.
Objectives: the aim of this research line will be to investigate the mechanisms involved in mitochondrial biogenesis during ischemia/reperfusion with particular regard to the evaluation of:
(1) the changes in mitochondrial fission and fusion; (2) the changes in the expression of protein members of mitochondrial electron transport chain (ETC); (3) the role played by AKAP 121 and mitochondrial Na+/Ca2+ exchanger (NCX3) in the regulation of mitochondrial biogenesis.
Methods: The experiments of the present research line are performed in primary cultures of cortical neurons exposed to OGD. Confocal microscopy is used to assess mitochondrial morphology (fission and fusion) and to detect changes in mitochondrial membrane potential and calcium concentration. The activity of proteins member of the mitochondrial electron transport is evaluated by Blu Native Polyacrylamide Gel Electrophoresys (BN PAGE). Western Blotting analysis is used to evaluate protein expression.
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
Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nisticò R, Scorziello A, Savoia C, Garbi C, Annunziato L, Feliciello A (2011) Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 13:412-22
Valsecchi V, Pignataro G, Del Prete A, Sirabella R, Matrone C, Boscia F, Scorziello A, Sisalli MJ, Esposito E, Zambrano N, Di Renzo G, Annunziato L (2011) NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke 42:754-63
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
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
Pignataro G, Scorziello A, Di Renzo G, Annunziato L (2009) Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy. FEBS J. 276:46-57
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
Carlucci A, Adornetto A, Scorziello A, Viggiano D, Foca M, Cuomo O, Annunziato L, Gottesman M, Feliciello A (2008) "Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia". EMBO J. 27:1073-84
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
Scorziello A, Santillo M, Adornetto A, Dell'aversano C, Sirabella R, Damiano S, Canzoniero LM, Renzo GF, Annunziato L (2007) "NO-induced neuroprotection in ischemic preconditioning stimulates mitochondrial Mn-SOD activity and expression via RAS/ERK1/2 pathway". J Neuroch 103:1472-80
Pannaccione A, Boscia F, Scorziello A, Adornetto A, Castaldo P, Sirabella R, Taglialatela M, Di Renzo G, Annunziato L (2007) "Up-regulation and increased activity of KV3.4 channels and its accessory subunit MIRP2 induced by amyloid peptide is involved in apoptotic neuronal death. Mol Pharm 72:665-73
Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nisticò R, Scorziello A, Savoia C, Garbi C, Annunziato L, Feliciello A (2011) Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 13:412-22
Valsecchi V, Pignataro G, Del Prete A, Sirabella R, Matrone C, Boscia F, Scorziello A, Sisalli MJ, Esposito E, Zambrano N, Di Renzo G, Annunziato L (2011) NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke 42:754-63
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
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
Pignataro G, Scorziello A, Di Renzo G, Annunziato L (2009) Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy. FEBS J. 276:46-57
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
Carlucci A, Adornetto A, Scorziello A, Viggiano D, Foca M, Cuomo O, Annunziato L, Gottesman M, Feliciello A (2008) "Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia". EMBO J. 27:1073-84
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
Scorziello A, Santillo M, Adornetto A, Dell'aversano C, Sirabella R, Damiano S, Canzoniero LM, Renzo GF, Annunziato L (2007) "NO-induced neuroprotection in ischemic preconditioning stimulates mitochondrial Mn-SOD activity and expression via RAS/ERK1/2 pathway". J Neuroch 103:1472-80
Pannaccione A, Boscia F, Scorziello A, Adornetto A, Castaldo P, Sirabella R, Taglialatela M, Di Renzo G, Annunziato L (2007) "Up-regulation and increased activity of KV3.4 channels and its accessory subunit MIRP2 induced by amyloid peptide is involved in apoptotic neuronal death. Mol Pharm 72:665-73
Project Title:
Project Title:
Molecular mechanisms involved in mitochondrial biogenesis in cellular models of ischemia/reperfusion
Mitochondrial biogenesis is an extremely complex process which involve the coordinated expression of mitochondrial and nuclear genes as well as the transport of nuclear gene products into mitochondria. Although the mechanisms involved in this process have been object of intensive studies during the last 20 years, the detailed mechanisms of the process are not yet completely clarified. What is known is that calcium ions are necessary to activate protein kinases able to recruit transcriptional factors and co-activators which in turn promote genes transcription and the expression of mitochondrial proteins. Moreover, this phenomenon is also associated to changes in mitochondrial morphology known as mitochondrial fission and fusion. The balance between these events is essential to the right mitochondrial function, and an impairment in the mechanisms involved in mitochondrial biogenesis might be involved in the pathogenesis of many neurodegenerative disease.
Objectives: the aim of this project will be to investigate the mechanisms involved in mitochondrial biogenesis during ischemia/reperfusion. To address this issue experiments will be performed:
(1) to evaluate whether changes in mitochondrial fission and fusion might be involved in the pathogenesis of ischemic damage; (2) to investigate changes in the expression of protein members of mitochondrial electron transport chain (ETC) in cells exposed to anoxic insults; (3) to investigate the role played by AKAP 121 and mitochondrial Na+/Ca2+ exchanger (NCX3) in the molecular mechanisms involved in the control of mitochondrial biogenesis during ischemia.
Methods: The experiments of the present project will be conducted in primary coltures of cortical neurons exposed to OGD. Confocal microscopy will be used to asses mitochondrial morphology (fission and fusion) and to detect changes in mitochondrial membrane potential and calcium concentration. The activity of proteins member of the mitochondrial electron transport will be evaluated by Blu Native Polyacrylamide Gel Electrophoresys (BN PAGE). Western Blotting analysis will be used to evaluate protein expression.
Objectives: the aim of this project will be to investigate the mechanisms involved in mitochondrial biogenesis during ischemia/reperfusion. To address this issue experiments will be performed:
(1) to evaluate whether changes in mitochondrial fission and fusion might be involved in the pathogenesis of ischemic damage; (2) to investigate changes in the expression of protein members of mitochondrial electron transport chain (ETC) in cells exposed to anoxic insults; (3) to investigate the role played by AKAP 121 and mitochondrial Na+/Ca2+ exchanger (NCX3) in the molecular mechanisms involved in the control of mitochondrial biogenesis during ischemia.
Methods: The experiments of the present project will be conducted in primary coltures of cortical neurons exposed to OGD. Confocal microscopy will be used to asses mitochondrial morphology (fission and fusion) and to detect changes in mitochondrial membrane potential and calcium concentration. The activity of proteins member of the mitochondrial electron transport will be evaluated by Blu Native Polyacrylamide Gel Electrophoresys (BN PAGE). Western Blotting analysis will be used to evaluate protein expression.
Project Title:
Mitochondrial bioenergetics during cerebral ischemic preconditioning and postconditioning
In vivo and in vitro studies showed that neurons exposed to a brief non-injurious anoxia develop resistance against longer toxic anoxic insults, a phenomenon termed preconditioning. Interestingly, further studies showed that a similar protection is obtained with ischemic postconditioning, a condition obtained when a brief episode of subletal anoxia is applied after a toxic anoxic stimulus. The mechanisms involved in the protection mediated by preconditioning and postconditioning are so far not well characterized but seem to involve PKA, growth factors, ROS production, NFkB, and activation of the ERK1/2 RAS pathway.
Objectives: the aim of this study will be to investigate the molecular mechanisms activated by ischemic pre- and post-conditioning with particular regard to the role played by mitochondria in the regulation of ionic cellular homeostasis and free radical production in cellular models of ischemic pre- and post-conditioning. Experiments will be performed in these models in order to evaluate:
1. The effect of pre- and post-conditioning on neuronal survival
2. The effect of pre- and post-conditioning on mitochondrial membrane potential and on the expression of mitochondrial related proteins
3. The effect of pre- and post-conditioning on the activity and expression of specific proteins involved in nucleus/mitochondrion communication such as the nuclear transcription factors NRF-1 e 2 and the nuclear co-activators peroxisome proliferator-activated receptor-�� coattivator-1�� (PGC-1�)
4. The effect of pre- and post-conditioning on the expression and activity of mitochondrial proteins involved in energy production and in the control of mitochondrial membrane potential and calcium concentration such as NCX 3 and AKAP121.
Objectives: the aim of this study will be to investigate the molecular mechanisms activated by ischemic pre- and post-conditioning with particular regard to the role played by mitochondria in the regulation of ionic cellular homeostasis and free radical production in cellular models of ischemic pre- and post-conditioning. Experiments will be performed in these models in order to evaluate:
1. The effect of pre- and post-conditioning on neuronal survival
2. The effect of pre- and post-conditioning on mitochondrial membrane potential and on the expression of mitochondrial related proteins
3. The effect of pre- and post-conditioning on the activity and expression of specific proteins involved in nucleus/mitochondrion communication such as the nuclear transcription factors NRF-1 e 2 and the nuclear co-activators peroxisome proliferator-activated receptor-�� coattivator-1�� (PGC-1�)
4. The effect of pre- and post-conditioning on the expression and activity of mitochondrial proteins involved in energy production and in the control of mitochondrial membrane potential and calcium concentration such as NCX 3 and AKAP121.