• Jin-Yi Hou, Xiao-Ling Zhou, Xiao-Yuan Wang, Jia Liang, and Qun Xue.
• Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Acupuncture and Moxibustion, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu 221002, China.
• Neuroscience. 2023 Feb 21; 512: 596959-69.

AbstractPeroxiredoxin-6 (PRDX6), a member of the peroxiredoxin family, has progressively emerged as a possible therapeutic target for a variety of brain diseases, particularly Alzheimer's disease and ischemic stroke. However, the role of PRDX6 in neurons under ischemic conditions has remained elusive. Here, we found that astrocytes could release PRDX6 extracellularly after OGD/R, and that PRDX6 release actually worsened neuroapoptosis under OGD/R. We discovered a unique PRDX6/RAGE/JNK signaling pathway that contributes to the effect of neuroapoptosis. We applied a specific inhibitor of the RAGE signaling pathway in a mouse MCAO model and observed significant alterations in animal behavior. Considered together, our findings show the crucial role of the astrocyte-released PRDX6 in the process of neuroapoptosis caused by OGD/R, and could provide novel insights for investigating the molecular mechanism of protecting brain function from ischemia-reperfusion injury.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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