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 language | English (US) |
|---|---|
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
Fingerprint
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 journal › Article
}
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 -