NeuroMolecular Medicine

, Volume 12, Issue 2, pp 149–163

A Clear and Present Danger: Endogenous Ligands of Toll-like Receptors

  • Jacob A. Sloane
  • Daina Blitz
  • Zachary Margolin
  • Timothy Vartanian
Review Paper

DOI: 10.1007/s12017-009-8094-x

Cite this article as:
Sloane, J.A., Blitz, D., Margolin, Z. et al. Neuromol Med (2010) 12: 149. doi:10.1007/s12017-009-8094-x

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.

Keywords

Toll-like receptors Innate immunity Heat shock proteins Hyaluronan HMGB1 Heparin sulfate Necrosis 

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Jacob A. Sloane
    • 1
  • Daina Blitz
    • 1
    • 2
  • Zachary Margolin
    • 1
    • 2
  • Timothy Vartanian
    • 2
  1. 1.Department of NeurologyBeth Israel Deaconess Medical Center, Center for Life Sciences, Rm. 628BostonUSA
  2. 2.Department of Neurology/NeuroscienceWeill Cornell Medical CollegeNew YorkUSA