Chao Wang, Jie Zhang, Junchun Tang, Yi-Yi Li, YanXia Gu, Ying Yu, Jing Xiong, Xueqing Zhao, Zheng Zhang, Ting-Ting Li, Jutao Chen, Qi Wan, Zhaohui Zhang
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...
April 16, 2018: Experimental Neurology