Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders

Abstract

Toll-like receptors (TLRs), a class of pattern recognition proteins, play an integral role in the modulation of systemic inflammatory responses. Cerebrovascular diseases (CVDs) are a group of pathological conditions that temporarily or permanently affect the brain tissue mostly via the decrease of oxygen and glucose supply. TLRs have a critical role in the activation of inflammatory cascades following hypoxic-ischemic events and subsequently contribute to neuroprotective or detrimental effects of CVD-induced neuroinflammation. The TLR signaling pathway and downstream cascades trigger immune responses via the production and release of various inflammatory mediators. The present review describes the modulatory role of the TLR signaling pathway in the inflammatory responses developed following various CVDs and discusses the potential benefits of the modulation of different TLRs in the improvement of functional outcomes after brain ischemia.

Keywords: brain; cell injury; chemokines; inflammatory mediators; stroke.

Figure 1

Diagrammatic representation of the Toll-like receptor (TLRs) signaling pathways. TLRs are expressed in neurons, microglia, astrocytes, oligodendrocytes as well as neural stem cells. DAMPs: Damage-associated molecular patterns; LPS: Lipopolysaccharide; dsDNA: Double-stranded DNA; dsRNA, Double-stranded RNA; ssRNA: Single-stranded RNA; MyD88: Myeloid differentiation primary response 88; PAMPs: Pathogen-associated molecular patterns; NF-kB: nuclear factor kappa B; IRF: Interferon regulatory factor; TRIF: TIR-domain-containing adapter inducing IFN-β.