• Tingting Wang, Ying Xue, Yumei Li, Sihao Gao, Li Peng, Yong Zhao, and Shanshan Yu.
• Department of Pathology, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, People's Republic of China; Department of Pathology, The Lu'an Hospital Affiliated of Anhui Medical University, 237000 Anhui, People's Republic of China; Department of Pathology, The Lu' an People's Hospital, 237000 Anhui, People's Republic of China.
• Neuroscience. 2022 Nov 10; 504: 334633-46.

AbstractDJ-1 plays a neuroprotective role in cerebral ischemia- reperfusion (I/R) injury and participates in the apoptosis of brain nerve cells, but the underlying mechanism is unclear. We explored the molecular pathways underlying this role using in vivo and in vitro approaches. Middle cerebral artery occlusion- reperfusion (MCAO/R) rat models and oxygen- glucose deprivation- reoxygenation (OGD/R) HAPI cell cultures were used to simulate cerebral ischemia-reperfusion injury. The interaction between DJ-1 and Notch1 was enhanced after MCAO/R in rats. After treatment of rats with DJ-1 siRNA, the expression of Notch1 and Nrf2 was down-regulated, and apoptosis was promoted. In contrast, the DJ-1 based peptide ND-13 upregulated the expression of Notch1 and Nrf2, and prevented apoptosis. In vitro, the Notch1 signaling pathway inhibitor DAPT reversed the neuroprotective effect of ND-13 and promoted apoptosis, weakened the interaction between DJ-1 and Notch1, and decreased the expression of proteins in the Notch1 and Nrf2 pathways. Thus, we found that DJ-1 inhibits apoptosis by regulating the Notch1 signaling pathway and Nrf2 expression in cerebral I/R injury. These results imply that DJ-1 is a potential therapeutic target for cerebral I/R injury.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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