title: The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia.
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.
authors.affiliation: School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia. fongchan.choy@adelaide.edu.au.
authors.forename: Fong Chan
authors.initials: FC
authors.lastname: Choy
authors.affiliation: School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia. thomas.klaric@alumni.adelaide.edu.au.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Klarić
authors.affiliation: School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. simon.koblar@adelaide.edu.au.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Koblar
authors.affiliation: School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia. Martin.Lewis@sahmri.com.|School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. Martin.Lewis@sahmri.com.|South Australian Health &amp; Medical Research Institute, North Terrace, Adelaide, SA 5005, Australia. Martin.Lewis@sahmri.com.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Lewis
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C481603:NPAS4 protein, human
keywords: Npas4; apoptosis; ischemic stroke; neuroinflammation; neuroprotection