title: A clear and present danger: endogenous ligands of Toll-like receptors.
abstract: Neurologic disease promoted by microbial pathogens, sterile injury, or neurodegeneration rapidly induces innate immunity in adjacent healthy tissue, which in turn contributes extensively to neurologic injury. With more recent focus on innate immune processes, it appears that necrotic, but not apoptotic, death mechanisms provoke inflammatory responses likely due to the release or production of endogenous ligands that activate resident immune cells of the central nervous system. These ligands comprise a diverse set of proteins, nucleic acids, and glycosaminoglycans, including heat shock proteins, HMGB1, RNA, DNA, hyaluronan, and heparin sulfate, that stimulate innate immune mechanisms largely through Toll-like receptors (TLRs). The blockade of interactions between endogenous ligands and TLRs may enable neuroprotective therapeutic strategies for a variety of neurologic diseases.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Center for Life Sciences, 330 Brookline Ave, Boston, MA 02215, USA. jsloane@bidmc.harvard.edu
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Sloane
authors.forename: Daina
authors.initials: D
authors.lastname: Blitz
authors.forename: Zachary
authors.initials: Z
authors.lastname: Margolin
authors.forename: Timothy
authors.initials: T
authors.lastname: Vartanian
mesh_terms: D017209:Apoptosis; D002490:Central Nervous System / Q000276:immunology / Q000502:physiology; D002493:Central Nervous System Diseases / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008024:Ligands; D009336:Necrosis; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D010586:Phagocytes / Q000502:physiology; D051193:Toll-Like Receptors / Q000276:immunology / Q000502:physiology*; D014527:Uric Acid / Q000378:metabolism; D014947:Wounds and Injuries / Q000503:physiopathology
chemical_list: D006360:Heat-Shock Proteins; D008024:Ligands; D051193:Toll-Like Receptors; D014527:Uric Acid