Toll-like Receptor 2: A Novel Therapeutic Target for Ischemic White Matter Injury and Oligodendrocyte Death

Despite paramount clinical significance of white matter stroke, there is a paucity of researches on the pathomechanism of ischemic white matter damage and accompanying oligodendrocyte (OL) death. Therefore, a large gap exists between clinical needs and laboratory researches in this disease entity. Recent works have started to elucidate cellular and molecular basis of white matter injury under ischemic stress. In this paper, we briefly introduce white matter stroke from a clinical point of view and review pathophysiology of ischemic white matter injury characterized by OL death and demyelination. We present a series of evidence that Toll-like receptor 2 (TLR2), one of the membranous pattern recognition receptors, plays a cell-autonomous protective role in ischemic OL death and ensuing demyelination. Moreover, we also discuss our recent findings that its endogenous ligand, high-mobility group box 1 (HMGB1), is released from dying OLs and exerts autocrine trophic effects on OLs and myelin sheath under ischemic condition. We propose that modulation of TLR2 and its endogenous ligand HMGB1 can be a novel therapeutic target for ischemic white matter disease.