TRAF1 is a critical regulator of cerebral ischaemia–reperfusion injury and neuronal death

Yan-Yun Lu, Zuo-Zhi Li, Ding-Sheng Jiang, Lang Wang, Yan Zhang, Ke Chen, Xiao-Fei Zhang, Yi Liu, Guo-Chang Fan, Yingjie Chen, Qinglin Yang, Yan Zhou, Xiao-Dong Zhang, Liu De-Pei and Hongliang Li ()
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Yan-Yun Lu: Renmin Hospital of Wuhan University
Zuo-Zhi Li: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College
Ding-Sheng Jiang: Renmin Hospital of Wuhan University
Lang Wang: Renmin Hospital of Wuhan University
Yan Zhang: Renmin Hospital of Wuhan University
Ke Chen: College of Life Sciences, Wuhan University
Xiao-Fei Zhang: College of Life Sciences, Wuhan University
Yi Liu: College of Life Sciences, Wuhan University
Guo-Chang Fan: University of Cincinnati
Yingjie Chen: University of Minnesota
Qinglin Yang: University of Alabama at Birmingham
Yan Zhou: College of Life Sciences, Wuhan University
Xiao-Dong Zhang: College of Life Sciences, Wuhan University
Liu De-Pei: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College
Hongliang Li: Renmin Hospital of Wuhan University

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: Abstract Stroke is a leading global cause of mortality and disability. Less than 5% of patients are able to receive tissue plasminogen activator thrombolysis within the necessary timeframe. Focusing on the process of neuronal apoptosis in the penumbra, which lasts from hours to days after ischaemia, appears to be promising. Here we report that tumour necrosis factor receptor-associated factor 1 (TRAF1) expression is markedly induced in wild-type mice 6 h after stroke onset. Using genetic approaches, we demonstrate that increased neuronal TRAF1 leads to elevated neuronal death and enlarged ischaemic lesions, whereas TRAF1 deficiency is neuroprotective. In addition, TRAF1-mediated neuroapoptosis correlates with the activation of the JNK pro-death pathway and inhibition of the Akt cell survival pathway. Finally, TRAF1 is found to exert pro-apoptotic effects via direct interaction with ASK1. Thus, ASK1 positively and negatively regulates the JNK and Akt signalling pathways, respectively. Targeting the TRAF1/ASK1 pathway may provide feasible therapies for stroke long after onset.

Date: 2013
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DOI: 10.1038/ncomms3852

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