Peroxiredoxin-6 Released by Astrocytes Contributes to Neuroapoptosis During Ischemia.

[Display omitted] • OGD/R-induced astrocytes damaged and released PRDX6. • The release of PRDX6 aggravated the neuroapoptosis suffering OGD/R. • The mechanism underlying PRDX6 release could be linked to aiPLA2 activities. • PRDX6's pro-apoptotic role in neurons may be associated with RAGE and JNK signaling pathways. Peroxiredoxin-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. [ABSTRACT FROM AUTHOR]