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The Role of Npas4 in Neuroprotection and Neurogenesis

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eview The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia Fong Chan Choy 1, Thomas S. Klari´c 1, Simon A. Koblar 2 and Martin D. Lewis 1,2,3,* Received: 31 August 2015; Accepted: 16 November 2015; Published: 4 December 2015 Academic Editor: Chris Sobey 1 School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; [email protected] (F.C.C.); [email protected] (T.S.K.) 2 School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia; [email protected] 3 South Australian Health & Medical Research Institute, North Terrace, Adelaide, SA 5005, Australia * Correspondence: [email protected]; Tel.: +61-8-8128-4703 Abstract: Stroke is one of the leading causes of death and adult disability in the world. Although many molecules have been documented to have a neuroprotective effect, the majority of these molecules failed to improve the neurological outcomes for patients with brain ischemia. It has been proposed that neuroprotection alone may, in fact, not be adequate for improving the prognosis of ischemic stroke. Neuroprotectants that can regulate other processes which occur in the brain during ischemia could potentially be targets for the development of effective therapeutic interventions in stroke. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an activity-dependent transcription factor whose expression is induced in various brain insults, including cerebral ischemia. It has been shown that Npas4 plays an important role in protecting neurons against many types of neurodegenerative insult. Recently, it was demonstrated that Npas4 indeed has a neuroprotective role in ischemic stroke and that Npas4 might be involved in modulating the cell death pathway and inflammatory response. In this review, we summarize the current knowledge of the roles that Npas4 may play in neuroinflammation and ischemia. Understanding how ischemic lesion size in stroke may be reduced through modulation of Npas4-dependent apoptotic and inflammatory pathways could lead to the development of new stroke therapies. Keywords: apoptosis; ischemic stroke; neuroinflammation; neuroprotection; Npas4 1. Introduction Stroke is the second leading single cause of death and the most common cause of long-term disability in the adult population worldwide [1]. Ischemic stroke is more prevalent than that of hemorrhagic stroke, accounting for approximately 87% of all strokes [2]. Cerebral ischemia occurs as a result of
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