The AAA + ATPase Thorase is neuroprotective against ischemic injury

Jianmin Zhang, Jia Yang, Huaishan Wang, Omar Sherbini, Matthew J. Keuss, George K.E. Umanah, Emily Ling Lin Pai, Zhikai Chi, Kaisa M.A. Paldanius, Wei He, Hong Wang, Shaida A. Andrabi, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Neuronal preconditioning in vitro or in vivo with a stressful but non-lethal stimulus leads to new protein expression that mediates a profound neuroprotection against glutamate excitotoxicity and experimental stroke. The proteins that mediate neuroprotection are relatively unknown and under discovery. Here we find that the expression of the AAA + ATPase Thorase is induced by preconditioning stimulation both in vitro and in vivo. Thorase provides neuroprotection in an ATP-dependent manner against oxygen–glucose deprivation (OGD) neurotoxicity or glutamate N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in vitro. Knock-down of Thorase prevents the establishment of preconditioning induced neuroprotection against OGD or NMDA neurotoxicity. Transgenic overexpression of Thorase provides neuroprotection in vivo against middle cerebral artery occlusion (MCAO)-induced stroke in mice, while genetic deletion of Thorase results in increased injury in vivo following stroke. These results define Thorase as a neuroprotective protein and understanding Thorase signaling could offer a new therapeutic strategy for the treatment of neurologic disorders.

Original languageEnglish (US)
Pages (from-to)1836-1848
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume39
Issue number9
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

Keywords

  • AAA + ATPase
  • ATAD1
  • neuroprotection
  • preconditioning
  • stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Zhang, J., Yang, J., Wang, H., Sherbini, O., Keuss, M. J., Umanah, G. K. E., Pai, E. L. L., Chi, Z., Paldanius, K. M. A., He, W., Wang, H., Andrabi, S. A., Dawson, T. M., & Dawson, V. L. (2019). The AAA + ATPase Thorase is neuroprotective against ischemic injury. Journal of Cerebral Blood Flow and Metabolism, 39(9), 1836-1848. https://doi.org/10.1177/0271678X18769770