The AAA + ATPase Thorase is Neuroprotective Against Ischemic Injury

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2018 Apr 17

PMID 29658368

Citations 7

Authors

Jianmin Zhang

Jia Yang

Huaishan Wang

Omar Sherbini

Matthew J Keuss

George Ke Umanah

Emily Ling-Lin Pai

Zhikai Chi

Kaisa Ma Paldanius

Wei He

Hong Wang

Shaida A Andrabi

Ted M Dawson

Valina L Dawson

Affiliations

Soon will be listed here.

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.

Citing Articles

ATAD1 Regulates Neuronal Development and Synapse Formation Through Tuning Mitochondrial Function.

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Thorase deficiency causes both Aβ accumulation and tau hyperphosphorylation in mouse brain.

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Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior.

Li C, Zhang H, Tong K, Cai M, Gao F, Yang J Cells. 2023; 12(16).

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Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction.

Winter J, Fresenius H, Cunningham C, Wei P, Keys H, Berg J Elife. 2022; 11.

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ATPase Thorase Deficiency Causes α-Synucleinopathy and Parkinson's Disease-like Behavior.

Gao F, Zhang H, Yang J, Cai M, Yang Q, Wang H Cells. 2022; 11(19).

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