Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Cinzia Severini, Roberta Lattanzi, Daniela Maftei, Veronica Marconi, Maria Teresa Ciotti, Pamela Petrocchi Passeri, Fulvio Florenzano, Ester Del Duca, Silvia Caioli, Cristina Zona, Gianfranco Balboni, Severo Salvadori, Robert Nistico, Lucia Negri

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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 Aβ1-42-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.

Original languageEnglish
Article number15301
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Oct 19 2015

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Severini, C., Lattanzi, R., Maftei, D., Marconi, V., Ciotti, M. T., Petrocchi Passeri, P., Florenzano, F., Del Duca, E., Caioli, S., Zona, C., Balboni, G., Salvadori, S., Nistico, R., & Negri, L. (2015). Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity. Scientific Reports, 5, [15301]. https://doi.org/10.1038/srep15301