小胶质细胞
衰老
天冬酰胺
化学
神经科学
生物化学
细胞生物学
生物
酶
免疫学
炎症
作者
Ouwen Qiu,Jing Zhao,Zhonggang Shi,Huan Li,Siyuan Wang,Keman Liao,Monica Tang,Jieqiong Xie,Xi Shan Hao,Wenrui Zhang,Li Zhou,Xi Yang,Zhiyi Zhou,Li‐Yan Xu,Renhua Huang,Yanwei Miao,Yongming Qiu,Yingying Lin
出处
期刊:iScience
[Elsevier]
日期:2024-05-01
卷期号:27 (5): 109698-109698
标识
DOI:10.1016/j.isci.2024.109698
摘要
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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