A clear and present danger: endogenous ligands of Toll-like receptors

Neuromolecular Med. 2010 Jun;12(2):149-63. doi: 10.1007/s12017-009-8094-x. Epub 2009 Oct 14.


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.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Central Nervous System / immunology
  • Central Nervous System / physiology
  • Central Nervous System Diseases / pathology
  • Central Nervous System Diseases / physiopathology
  • Extracellular Matrix / physiology
  • Heat-Shock Proteins / physiology
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Ligands
  • Necrosis
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Phagocytes / physiology
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / physiology*
  • Uric Acid / metabolism
  • Wounds and Injuries / physiopathology


  • Heat-Shock Proteins
  • Ligands
  • Toll-Like Receptors
  • Uric Acid