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.

中文翻译：

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Toll样受体2：缺血性白质损伤和少突胶质细胞死亡的新型治疗靶点。

尽管白质中风具有极其重要的临床意义，但对缺血性白质损害及其伴随的少突胶质细胞（OL）死亡的发病机理的研究很少。因此，在该疾病实体的临床需求和实验室研究之间存在很大的差距。最近的工作已经开始阐明缺血应激下白质损伤的细胞和分子基础。在本文中，我们从临床角度简要介绍了白质中风，并回顾了以OL死亡和脱髓鞘为特征的缺血性白质损伤的病理生理学。我们提供了一系列证据，即膜样模式识别受体之一的Toll样受体2（TLR2）在缺血性OL死亡和随后的脱髓鞘作用中具有细胞自主保护作用。而且，我们还讨论了我们最近的发现，即其内源性配体高迁移率族盒1（HMGB1）从垂死的OLs中释放，并在缺血条件下对OLs和髓鞘产生自分泌营养作用。我们建议调节TLR2及其内源性配体HMGB1可以作为缺血性白质病的新型治疗靶标。