title: Ras family small GTPase-mediated neuroprotective signaling in stroke.
abstract: Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of stroke, the overall mechanisms governing the balance between cell survival and death are not well-defined. Ras family small GTPases are activated following ischemic insults, and in turn, serve as intrinsic switches to regulate neuronal survival and regeneration. Their ability to integrate diverse intracellular signal transduction pathways makes them critical regulators and potential therapeutic targets for neuronal recovery after stroke. This article highlights the contribution of Ras family GTPases to neuroprotective signaling cascades, including mitogen-activated protein kinase (MAPK) family protein kinase- and AKT/PKB-dependent signaling pathways as well as the regulation of cAMP response element binding (CREB), Forkhead box O (FoxO) and hypoxiainducible factor 1(HIF1) transcription factors, in stroke.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 S. Limestone St., Lexington, KY 40536-0509, USA. gshi2@uky.edu
authors.forename: Geng-Xian
authors.initials: GX
authors.lastname: Shi
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Andres
authors.forename: Weikang
authors.initials: W
authors.lastname: Cai
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D051858:Forkhead Transcription Factors; D051793:Hypoxia-Inducible Factor 1; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020559:Monomeric GTP-Binding Proteins