The AAA + ATPase Thorase is neuroprotective against ischemic injury

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

Research output: Contribution to journalArticle

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)
JournalJournal of Cerebral Blood Flow and Metabolism
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Adenosine Triphosphatases
Wounds and Injuries
Stroke
Glutamic Acid
Proteins
Middle Cerebral Artery Infarction
N-Methylaspartate
Nervous System Diseases
N-Methyl-D-Aspartate Receptors
Adenosine Triphosphate
Neuroprotection
In Vitro Techniques
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

The AAA + ATPase Thorase is neuroprotective against ischemic injury. / Zhang, Jianmin; Yang, Jia; Wang, Huaishan; Sherbini, Omar; Keuss, Matthew J.; Umanah, George; Pai, Emily Ling Lin; Chi, Zhikai; Paldanius, Kaisa M.A.; He, Wei; Wang, Hong; Andrabi, Shaida A.; Dawson, Ted M; Dawson, Valina.

In: Journal of Cerebral Blood Flow and Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

Zhang, J, Yang, J, Wang, H, Sherbini, O, Keuss, MJ, Umanah, G, Pai, ELL, Chi, Z, Paldanius, KMA, He, W, Wang, H, Andrabi, SA, Dawson, TM & Dawson, V 2018, 'The AAA + ATPase Thorase is neuroprotective against ischemic injury', Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X18769770
Zhang, Jianmin ; Yang, Jia ; Wang, Huaishan ; Sherbini, Omar ; Keuss, Matthew J. ; Umanah, George ; Pai, Emily Ling Lin ; Chi, Zhikai ; Paldanius, Kaisa M.A. ; He, Wei ; Wang, Hong ; Andrabi, Shaida A. ; Dawson, Ted M ; Dawson, Valina. / The AAA + ATPase Thorase is neuroprotective against ischemic injury. In: Journal of Cerebral Blood Flow and Metabolism. 2018.
@article{4c29a9ad329c4cd59864b828c9389e6a,
title = "The AAA + ATPase Thorase is neuroprotective against ischemic injury",
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.",
keywords = "AAA + ATPase, ATAD1, neuroprotection, preconditioning, stroke",
author = "Jianmin Zhang and Jia Yang and Huaishan Wang and Omar Sherbini and Keuss, {Matthew J.} and George Umanah and Pai, {Emily Ling Lin} and Zhikai Chi and Paldanius, {Kaisa M.A.} and Wei He and Hong Wang and Andrabi, {Shaida A.} and Dawson, {Ted M} and Valina Dawson",
year = "2018",
month = "1",
day = "1",
doi = "10.1177/0271678X18769770",
language = "English (US)",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - The AAA + ATPase Thorase is neuroprotective against ischemic injury

AU - Zhang, Jianmin

AU - Yang, Jia

AU - Wang, Huaishan

AU - Sherbini, Omar

AU - Keuss, Matthew J.

AU - Umanah, George

AU - Pai, Emily Ling Lin

AU - Chi, Zhikai

AU - Paldanius, Kaisa M.A.

AU - He, Wei

AU - Wang, Hong

AU - Andrabi, Shaida A.

AU - Dawson, Ted M

AU - Dawson, Valina

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - AAA + ATPase

KW - ATAD1

KW - neuroprotection

KW - preconditioning

KW - stroke

UR - http://www.scopus.com/inward/record.url?scp=85045426732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045426732&partnerID=8YFLogxK

U2 - 10.1177/0271678X18769770

DO - 10.1177/0271678X18769770

M3 - Article

C2 - 29658368

AN - SCOPUS:85045426732

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

ER -