Lysophosphatidic acid induces neuronal cell death via activation of asparagine endopeptidase in cerebral ischemia-reperfusion injury

Lysophosphatidic acid induces neuronal cell death via activation of asparagine endopeptidase in... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Neurology Elsevier

Lysophosphatidic acid induces neuronal cell death via activation of asparagine endopeptidase in cerebral ischemia-reperfusion injury

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Inc.
ISSN
0014-4886
D.O.I.
10.1016/j.expneurol.2018.04.010
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Experimental NeurologyElsevier

Published: Aug 1, 2018

References

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