Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Department of Physiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences, Wuhan University School of Medicine, Wuhan, China.
Exp Neurol. 2018 Aug;306:1-9. doi: 10.1016/j.expneurol.2018.04.010. Epub 2018 Apr 17.
Lysophosphatidic acid (LPA), an extracellular signaling molecule, influences diverse biological events, including the pathophysiological process induced after ischemic brain injury. However, the molecular mechanisms mediating the pathological change after ischemic stroke remain elusive. Here we report that asparagine endopeptidase (AEP), a lysosomal cysteine proteinase, is regulated by LPA during stroke. AEP proteolytically cleaves tau and generates tauN368 fragments, triggering neuronal death. Inhibiting the generation of LPA reduces the expression of AEP and tauN368, and alleviates neuronal cell death. Together, this evidence indicates that the LPA-AEP pathway plays a key role in the pathophysiological process induced after ischemic stroke. Inhibition of LPA could be a useful therapeutic for treating neuronal injury after stroke.
溶血磷脂酸（LPA）是一种细胞外信号分子，影响多种生物学事件，包括缺血性脑损伤后诱导的病理生理过程。然而，介导缺血性中风后病理变化的分子机制仍不清楚。在这里，我们报告溶酶体半胱氨酸蛋白酶天冬酰胺内肽酶（AEP）在中风期间受 LPA 调节。AEP 蛋白水解切割 tau 并产生 tauN368 片段，触发神经元死亡。抑制 LPA 的产生可降低 AEP 和 tauN368 的表达，并减轻神经元细胞死亡。总之，这些证据表明 LPA-AEP 途径在缺血性中风后诱导的病理生理过程中起关键作用。抑制 LPA 可能是治疗中风后神经元损伤的一种有效方法。
