Toll-Like receptor tolerance as a mechanism for neuroprotection

Keri B. Vartanian, Mary Stenzel-Poore

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

It has been discovered recently that Toll-like receptors (TLRs) are key mediators of tissue injury in response to stroke. This revelation has identified a new target critical to understanding the underlying mechanisms of stroke injury and potential therapies. Much of the interest in TLRs centers around their ability to self-regulate-a process commonly referred to as "tolerance," wherein prior exposure to low-level TLR activation induces protection against a subsequent challenge that would otherwise cause damage. This endogenous process has been exploited in the setting of stroke. Recent studies show that TLR pathways can be reprogrammed via prior exposure to TLR ligands, leading to decreased infarct size and improved neurological outcomes in response to ischemic injury. Efforts to understand the molecular mechanisms of TLR reprogramming have led to the identification of multiple routes of TLR regulation including inhibitors that target signaling mediators, microRNAs that suppress genes posttranscriptionally, and epigenetic changes in chromatin remodeling that affect global gene regulation. In this review, we discuss the role of TLRs in mediating injury due to stroke, evidence for TLR-preconditioning-induced TLR reprogramming in response to stroke, and possible mechanisms of TLR-induced neuroprotection.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalTranslational Stroke Research
Volume1
Issue number4
DOIs
StatePublished - Dec 2010

Fingerprint

Toll-Like Receptors
Stroke
Wounds and Injuries
Neuroprotection
Chromatin Assembly and Disassembly
MicroRNAs
Epigenomics
Genes
Ligands

Keywords

  • Endotoxin tolerance
  • Neuroprotection
  • Stroke
  • Toll-like receptors

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

Cite this

Toll-Like receptor tolerance as a mechanism for neuroprotection. / Vartanian, Keri B.; Stenzel-Poore, Mary.

In: Translational Stroke Research, Vol. 1, No. 4, 12.2010, p. 252-260.

Research output: Contribution to journalArticle

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