Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (10): 2278-2284.doi: 10.4103/1673-5374.369116

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TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage

Hao-Xiang Wang1, #, Chang Liu2, #, Yuan-You Li1, Yi Cao3, Long Zhao4, Yan-Jie Zhao1, Zi-Ang Deng1, Ai-Ping Tong1, 5, *, Liang-Xue Zhou1, *   

  1. 1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; 2Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 3Department of Neurosurgery, Chengdu Second People’s Hospital, Chengdu, Sichuan Province, China; 4Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China; 5State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
  • Online:2023-10-15 Published:2023-03-29
  • Contact: Liang-Xue Zhou, MD, zhlxlll@163.com; Ai-Ping Tong, MD, aipingtong@scu.edu.cn.

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Abstract: Pyroptosis plays an important role in hemorrhagic stroke. Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) pathway. However, the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear. In this study, we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue. Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress, pyroptosis, and inflammation and protected neurons. The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation. 

Key words: ameliorating inflammation, endoplasmic reticulum stress, GPR120, GSDMD, hemorrhagic stroke, neurological function, NLRP3, pyroptosis, TUG-891, unfolded protein response