Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Jianyi Zhao
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Zhonggang Shi
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Huan Li
Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
Siyuan Wang
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Keman Liao
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Minchao Tang
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi 530021, P.R. China
Jieqiong Xie
Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Guangxi 530007, P.R. China
Xi Huang
Department of Digestive Oncology, Guangxi Medical University Cancer Hospital, Guangxi 530021, P.R. China
Wenrui Zhang
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Li Zhou
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Xi Yang
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Zhiyi Zhou
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Lei Xu
Department of Radiation, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Renhua Huang
Department of Radiation, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Yifeng Miao
Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China; Corresponding author
Yongming Qiu
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China; Corresponding author
Yingying Lin
Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China; Corresponding author
Summary: Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn−/−) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP’s involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn−/− primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.
