Giuseppe Pignataro
Giuseppe Pignataro
e-mail:
website: www.unina.it
affiliation: Università di Napoli Federico II
research area(s): Neuroscience
Course: Neurosciences
University/Istitution: Università di Napoli Federico II
Firts Name Giuseppe
Last Name Pignataro
Date of birth November 6th 1975
Place of birth San Mauro Marchesato (ITALY)

Professional address Division of Pharmacology, Department of Neuroscience, School of Medicine
University of Naples “Federico II” Naples (ITALY)

Education
2008 Medical Doctor degree, 110/100, School of Medicine, “Federico II” University of Naples, Italy.
2003 PhD degree in Neuroscience, School of Medicine, “Federico II” University of Naples, Italy.
1999 Degree in Medicinal Chemistry cum laude, School of Pharmacy, “Federico II” University of Naples, Italy.
Current Position
2007- Assistant Professor in Pharmacology, School of Medicine, “Federico II” University of Naples, Italy.

Expertise and main scientific interests
The research of Dr. Pignataro is aimed to study the molecular and cellular mechanisms underlying the phenomenon of neuronal damage induced by episodes of ischemia, with particular regard to the role of proteins able to modulate the homeostasis of sodium and calcium ions and involved in ischemic damage. These studies were conducted using microsurgery techniques to induce focal cerebral ischemia on small animals. He is able to study the effect of these animal-induced neurodegenerative disorders on genomic and proteomic rearrangement as well as to study phenotypic, and neurological characteristics of these animals. Over the years Dr. Pignataro has applied several microsurgical techniques to study the mechanisms underlying ischemic damage. In particular, few years ago he was able to measure for the first time intracerebral pH in freely moving mice, by using ad hoc built pH sensitive probes stereotassically implanted in ischemic mice (Pignataro et al., 2007, Brain). Furthermore, by means of in vivo antisense strategy, he discovered the role played by two ionic membrane transporters, NCX1 and NCX3, in mediating the stroke damage induced (Pignataro et al., 2004, Stroke). Finally, he identified a group of genetically modified stem cells, able to produce a great amount of adenosine, inducing a strong neuroprotection when transplanted into the brain of ischemic animals (Pignataro et al., 2007, JCBFM).
Ultimately, a considerable effort was devoted to the study of endogenous mechanisms of neuroprotection in order to identify promising new therapeutic strategies for treating brain ischemia. Within these studies, he identified and characterized a new mechanism of neuroprotection called endogenous Postconditioning. This phenomenon studied in an animal model of cerebral ischemia, which provides a controlled riperfusione subsequent to a strong ischemia is able to considerably ameliorate the size of the ischemic lesion (Pignataro et al., 2008, JCBFM). Recently, he demonstrated that the Sodium/Calcium Exchanger 3 and the Asic Sensing Ionic Channel 1a play a fundamental role in mediating ischemic postconditioning neuroprotection (Pignataro et al., 2010, JCBFM and Pignataro et al., 2010, JPPP).

Research Support
Ministry of Health, Ricerca sanitaria ordinario 2007, Title: ”Identification of vulnerability factors and pharmacological therapy of neuronal loss in Amyotrophic Lateral Sclerosis in human and transgenic animals”
Ministry of Health, Ricerca sanitaria ordinario 2007, Title: “Liquoral and plasmatic markers of synaptic degeneration in cognitive decline: a validation in the clinical practices and in animal models”
Ministry of Research and University 2009, Title:“ Ischemia Cerebrale e Modificazioni trascrizionali nell’unità neurovascolare: basi per l’identificazione di nuovi bersagli molecolari per agenti neuroprotettivi”
As clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. The concepts of ischemic preconditioning and postconditioning have been characterized.The concept of ischemic preconditioning lies on the observation that a brief non-injurious episode of ischemia is able to protect the brain from a subsequent lethal insult.
Surprisingly, it has been recently reported that modified reperfusion subsequent to a prolonged ischemic episode may also confer ischemic neuroprotection, a phenomenon termed postconditioning. A more suitable way to induce pre- or postconditioning is represented by the so-called remote conditioning, in which the sublethal hypoxic event is applied on an artery distant fom the brain, i.e. femoral artery.
Within the numerous mechanisms proposed to explain the neuroprotection mediated by preconditioning and postconditioning, a key role seems to be ascribed to the Mitogen Activated Kinases (MAPK), a family of kinases activated during reperfusion.

Objectives: (1) To evaluate the effect of preconditioning and postconditioning activated MAPK on the activity and expression of non-NMDA dependent ionic channels and membrane transporters involved in the progression of the ischemic lesion. (2) To evaluate the role played by NCX, a membrane protein family that controls cellular ionic homeostasis and that is involved in the progression of the ischemic damage, in the neuroprotection induced by local and remote preconditioning and postconditioning.

Methods: The experiments of the present project are carried out in rats exposed to transient occlusion of the cerebral middle artery (MCAO) and subjected to preconditioning and postconditioning. Western Blotting, RT-PCR and In situ Hybridization analysis will be used to evaluate protein and mRNA expression. The role played by NCX will be evacuate by using the in vivo silencing strategy to downregulate each NCX isoform espresse within the CNS.
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 GF; Annunziato L. (2008)Targeted Disruption of NCX3 Gene Leads to a Worsening of Ischemic Brain Damage. J Neurosci 30;28(5):1179-84
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 GF; Annunziato L. (2008)A Critical Role for the Potassium-Dependent Sodium/Calcium Exchanger NCKX2 in Protection Against Focal Ischemic Brain Damage. J Neurosci Feb 27;28(9):2053-63
Pignataro G, Scorziello A, Di Renzo GF, Annunziato L. (2009)Post-ischemic brain damage: effect of ischemic preconditioningand postconditioning and identification of potential candidates for stroke therapy. FEBS Journal 276:46-57
Zhan S; Zhao H; White A; Minami M; Pignataro G; Yang T; Zhu X; Lan J; Xiong ZG; Steiner D; Simon RP; Zhou A. (2009)Defective neuropeptide processing and ischemic brain injury - a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains. J Cereb Blood Flow Metab 29(4):698-706 Lusardi TA, Farr DA, Faulkner CL, Pignataro G, Yang T, Lan J, Simon RP, and Saugstad JA. (2010) Ischemic Peconditioning Regulates Expression of MicroRNAs and a redicted Target, MeCP2, in Mouse Cortex J Cereb Blood Flow Metab 30(4):744-756
Esposito F, Pignataro G, Di Renzo GF, Spinali A, Paccone A, Tedeschi G, Annunziato L. (2010) Alcohol increases spontaneous BOLD signal fluctuations in the visual network Neuroimage 53(2):534-543
Pignataro G; Esposito E; Cuomo O; Sirabella R; Boscia F; Di Renzo GF; and Annunziato L. (2011)The NCX3 isoform of the Na+/Ca2+ exchanger contributes to neuroprotection elicited by ischemic postconditioning J Cereb Blood Flow Metab 31(1):362-370
Pignataro G; Cuomo O; Esposito E; Sirabella R; Di Renzo GF; and Annunziato L.(2011) ASIC1a contributes to neuroprotection elicited by ischemic preconditioning and postconditioning. Int J Physiol Pathophysiol Pharmacol; 3(1):1-8
Valsecchi V*, Pignataro G*; Del Prete A; Sirabella R; Matrone C; Boscia F; Scorziello A; Sisalli MJ; Esposito E; Zambrano N; Di Renzo G; and Annunziato L. (2011) NCX1: a Novel Target Gene for Hypoxia Inducible Factor-1 in Ischemic Brain Preconditioning. Stroke 2 (3):754-763
Pignataro G, Capone D, Polichetti G, Vinciguerra A, Gentile A, Di Renzo G, Annunziato L. (2011) Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: current and emerging therapeutic options. Curr Opin Pharmacol. Jun 4.
Pignataro G, Boscia F, Esposito E, Sirabella R, Cuomo O, Vinciguerra A, Di Renzo G, Annunziato L.(2011) NCX1 and NCX3: Two new effectors of delayed preconditioning in brain ischemia. Neurobiol Dis. Oct 17
Lapi D, Vagnani S, Pignataro G, Esposito E, Paterni M, Colantuoni A.(2012)
Protective Effects of Quercetin on Rat Pial Microvascular Changes during Transient Bilateral Common Carotid Artery Occlusion and Reperfusion. Front Physiol. 3:32
Lapi D, Vagnani S, Pignataro G, Esposito E, Paterni M, Colantuoni A. (2012)Rat pial microvascular responses to transient bilateral common carotid artery occlusion and reperfusion: quercetin’s mechanism of action. Front Physiol. 3:99
Lanzillotta A*, Pignataro G*, Branca C, Cuomo O, Sarnico I, Benarese M, Annunziato L, Spano PF, Pizzi M. (2012) Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window. Neurobiol of Dis
Project Title:
Ischemic preconditioning and postconditioning: molecular mechanisms and therapeutic opportunities
The concepts of ischemic preconditioning and postconditioning have recently been characterized. In ischemic preconditioning a brief non-injurious episode of ischemia is able to protect the brain from a subsequent lethal insult.
Surprisingly, modified reperfusion subsequent to a prolonged ischemic episode may also confer ischemic neuroprotection, a phenomenon termed postconditioning. A more suitable way to induce pre- or postconditioning is represented by the so-called remote conditioning, in which the sublethal hypoxic event is applied on an artery distant fom the brain, i.e. femoral artery.
Within the numerous mechanisms proposed to explain the neuroprotection mediated by preconditioning and postconditioning, a key role seems to be ascribed to the Mitogen Activated Kinases (MAPK), a family of kinases activated during reperfusion.
Objectives: 1)To evaluate the effect of preconditioning and postconditioning activated MAPK on the activity and expression of non-NMDA dependent ionic channels and membrane transporters involved in the progression of the ischemic lesion. 2)To evaluate the role played by NCX, a membrane protein family that controls cellular ionic homeostasis and that is involved in the progression of the ischemic damage, in the neuroprotection induced by local and remote preconditioning and postconditioning.
Methods: The experiments of the present project are carried out in rats exposed to transient occlusion of the cerebral middle artery and subjected to preconditioning and postconditioning. Western Blotting, RT-PCR and In situ Hybridization analysis will be used to evaluate protein and mRNA expression. The role played by NCX will be evacuate by using the in vivo silencing strategy to downregulate each NCX isoform espresse within the CNS.