title: Microglia Function in the Central Nervous System During Health and Neurodegeneration.
abstract: Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110; email: mcolonna@pathology.wustl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; email: obutovsky@rics.bwh.harvard.edu.
authors.forename: Oleg
authors.initials: O
authors.lastname: Butovsky
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D001921:Brain / Q000502:physiology*; D002490:Central Nervous System; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D017628:Microglia / Q000502:physiology* / Q000637:transplantation; D019636:Neurodegenerative Diseases / Q000276:immunology*; D020078:Neurogenic Inflammation
chemical_list: D016207:Cytokines
keywords: homeostasis; microglia; neurodegeneration; phenotypes; receptors; regulation