Chao Wei, Zhongnan Xiao, Yanling Zhang, Zhaoli Luo, Dongyang Liu, Liye Hu, Danmin Shen, Meng Liu, Lei Shi, Xiaotong Wang, Ting Lan, Qingqing Dai, Jing Liu, Wen Chen, Yurui Zhang, Qingyu Sun, Weihua Wu, Peipei Wang, Chenguang Zhang, Junchi Hu, Chu Wang, Fei Yang, Qian Li
Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice...
May 8, 2024: Cell Death and Differentiation