title: Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity.
abstract: Bv8/Prokineticin 2 (PROK2) is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Among multiple biological roles demonstrated for PROK2, it was recently established that PROK2 is an insult-inducible endangering mediator for cerebral damage. Aim of the present study was to evaluate the PROK2 and its receptors' potential involvement in amyloid beta (Aβ) neurotoxicity, a hallmark of Alzheimer's disease (AD) and various forms of traumatic brain injury (TBI). Analyzing primary cortical cultures (CNs) and cortex and hippocampus from Aβ treated rats, we found that PROK2 and its receptors PKR1 and PKR2 mRNA are up-regulated by Aβ, suggesting their potential involvement in AD. Hence we evaluated if impairing the prokineticin system activation might have protective effect against neuronal death induced by Aβ. We found that a PKR antagonist concentration-dependently protects CNs against Aβ(1-42)-induced neurotoxicity, by reducing the Aβ-induced PROK2 neuronal up-regulation. Moreover, the antagonist completely rescued LTP impairment in hippocampal slices from 6 month-old Tg2576 AD mice without affecting basal synaptic transmission and paired pulse-facilitation paradigms. These results indicate that PROK2 plays a role in cerebral amyloidosis and that PROK2 antagonists may represent a new approach for ameliorating the defining pathology of AD.
authors.affiliation: Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 00143, Roma.|European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Severini
authors.affiliation: Department of Human Physiology and Pharmacology "Vittorio Erspamer", University of Roma "La Sapienza", P.za A. Moro 5, 00185 Roma.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lattanzi
authors.affiliation: Department of Human Physiology and Pharmacology "Vittorio Erspamer", University of Roma "La Sapienza", P.za A. Moro 5, 00185 Roma.
authors.forename: Daniela
authors.initials: D
authors.lastname: Maftei
authors.affiliation: Department of Human Physiology and Pharmacology "Vittorio Erspamer", University of Roma "La Sapienza", P.za A. Moro 5, 00185 Roma.
authors.forename: Veronica
authors.initials: V
authors.lastname: Marconi
authors.affiliation: Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 00143, Roma.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.affiliation: Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 00143, Roma.
authors.forename: Pamela
authors.initials: P
authors.lastname: Petrocchi Passeri
authors.affiliation: European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.affiliation: European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome.
authors.forename: Ester
authors.initials: E
authors.lastname: Del Duca
authors.affiliation: University of Rome "Tor Vergata" 00133 Rome.|IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, 00142 Roma.
authors.forename: Silvia
authors.initials: S
authors.lastname: Caioli
authors.affiliation: University of Rome "Tor Vergata" 00133 Rome.|IRCCS Fondazione Santa Lucia, Via Ardeatina, 306, 00142 Roma.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, 09124 Cagliari.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.affiliation: Department of Pharmaceutical Sciences, Università of Ferrara, Ferrara.
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.affiliation: European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome.|University of Rome "Tor Vergata" 00133 Rome.
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.affiliation: Department of Human Physiology and Pharmacology "Vittorio Erspamer", University of Roma "La Sapienza", P.za A. Moro 5, 00185 Roma.
authors.forename: Lucia
authors.initials: L
authors.lastname: Negri
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D021381:Protein Transport; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; D010446:Peptide Fragments; C486587:Prok2 protein, rat; D043562:Receptors, G-Protein-Coupled; C075222:amyloid beta-protein (1-42)