title: Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles.
abstract: Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial 'On' or 'Off' responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made toward deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, 'On' and 'Off' receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries.
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15240, USA. Electronic address: hux2@upmc.edu.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Anthony K F
authors.initials: AK
authors.lastname: Liou
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China.
authors.forename: Chengrui
authors.initials: C
authors.lastname: An
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Suenaga
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15240, USA. Electronic address: chenj2@upmc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology*; D006801:Humans; D017628:Microglia / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D020196:Trauma, Nervous System / Q000276:immunology*
chemical_list: D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D051192:Receptors, Pattern Recognition; D011983:Receptors, Purinergic; C408123:phosphatidylserine receptor
keywords: Central nervous system injuries; Microglia; Receptor