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Updated: May 9, 2026

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated
Ouwen Qiu1, Jianyi Zhao1, Zhonggang Shi1
1Brain Injury Center, Shanghai Institute of Head Trauma, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.
Abstract:
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.
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