title: Does Na⁺/Ca²⁺ exchanger, NCX, represent a new druggable target in stroke intervention?
abstract: Stroke causes a rapid cell death in the core of the injured region and triggers mechanisms in surrounding penumbra area that leads to changes in concentrations of several ions like intracellular Ca²⁺, Na⁺, H⁺, K⁺, and radicals such as reactive oxygen species and reactive nitrogen species. When a dysregulation of homeostasis of these messengers occurs, it can trigger cell death. In particular, it is widely accepted that a critical factor in determining neuronal death during cerebral ischemia is progressive dysregulation of Ca²⁺, Na⁺, K⁺, and H⁺ homeostasis that activate several death pathways, including oxidative and nitrosative stress, mitochondrial dysfunction, protease activation, and apoptosis. In the last decade, several seminal experimental works are markedly changing the scenario of research of principal players of an ischemic event. Indeed, some plasma membrane channels and transporters, involved in the control of Ca²⁺, Na⁺, K⁺, and H⁺ ion influx or efflux and, therefore, responsible for maintaining the homeostasis of these four cations, might function as crucial players in initiation of brain ischemic process. Indeed, these proteins, by regulating ionic homeostasis, may provide the molecular basis underlying glutamate-independent Ca²⁺ and Na⁺ overload mechanisms in neuronal ischemic cell death and, most importantly, may represent more suitable molecular targets for therapeutic intervention. Recently, a great deal of interest has been devoted to clarify the role of the plasma membrane protein known as Na⁺/Ca²⁺ exchanger, a transporter able to control Na⁺ and Ca²⁺ homeostasis. In this review, the pathophysiological role of NCX and its implication as a potential target in stroke intervention will be examined.
authors: Division Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via Pansini, 5, 80131, Naples, Italy.
authors: Giuseppe
authors: G
authors: Pignataro
authors: Rossana
authors: R
authors: Sirabella
authors: Serenella
authors: S
authors: Anzilotti
authors: Gianfranco
authors: G
authors: Di Renzo
authors: Lucio
authors: L
authors: Annunziato
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020521:Stroke / Q000235:genetics / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger