Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System

Toll-like receptors (TLRs) are type I transmembrane signaling molecules that are expressed in cells of the innate immune system. In these cells, TLRs function as pattern recognition receptors (PRR) that recognize specific molecular patterns derived from microorganisms. Upon activation, TLRs trigger a cascade of intracellular signaling pathways in innate immune cells, leading to the induction of inflammatory and innate immune responses, which in turn regulate adaptive immune responses. In the nervous system, different members of the TLR family are expressed on glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells) and neurons. Recently, increasing evidence has supported the idea that TLRs also recognize endogenous molecules that are released from damaged tissue, thereby regulating inflammatory responses and subsequent tissue repair. These findings imply that TLRs on glial cells may also be involved in the inflammatory response to tissue damage in the nervous system. In this review, we discuss recent studies on TLR expression in the cells of the nervous system and their roles in acute neurological disorders involving tissue damage such as strokes, traumatic spinal cord and brain injuries, and peripheral nerve injuries.