Dr. Zhong Chen/'s group published in Autophagy

In July 2014, Dr. Chen Zhong Research Group published their recent work on a novel neuroprotection of ER stress against cerebral ischemia by regulating autophagy. The present work is a successive investigation of a previous paper which was also published in this journal.

Cerebral ischemia is a leading cause of mortality and disability with few therapy. The patholgical mechanisms and potential therapeutic targets against brain ischemia are intensively studied in the past decades. Dr. Chen Zhong lab previously demonstrated that autophagy plays an important protective role in ischemic brains by clearancing damaged mitochondria (Zhang et al. Autophagy 2013 9(9): 1321-1333). Therefore, it is intriguing to postulate that mitophagy may be a novel therapeutic target against brian stroke.

For this reason, the researchers investigated several triggers of autophagy in the context of cerebral ischemia, in which they found that ER stress could be a potential manner to induce autophagy. Interestingly, they found that low dosage ER stressors reduced focal cerebral ischemia in mice and rescued OGD-treated neurons. Further investigations indicated that moderate ER stress during cerebral ischemia selectively triggered mitophagy by EIF2-alpha/ATF4 signaling, which subsequently upregulated Parkin expression and ultimately increased mitophagy. These results suggested, for the first time, that mitophagy can be a novel therapeutic strategy aginast brain stroke.

Zhang X, Yuan Y, Jiang L, Zhang J, Gao J, Shen Z, Zheng Y, Deng T, Yan H, Li W, Hou WW, Lu J, Shen Y, Dai H, Hu WW, Zhang Z, Chen Z. Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy. Autophagy. 2014 Oct 1;10(10):1801-13.