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

  • Neural Regen Res. 2023 Oct;18(10):2278-2284. doi: 10.4103/1673-5374.369116.
Hao-Xiang Wang  1 ,  Chang Liu  2 ,  Yuan-You Li  1 ,  Yi Cao  3 ,  Long Zhao  4 ,  Yan-Jie Zhao  1 ,  Zi-Ang Deng  1 ,  Ai-Ping Tong  5 ,  Liang-Xue Zhou  1
Affiliations
  • 1. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  • 2. Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3. Department of Neurosurgery, Chengdu Second People's Hospital, Chengdu, Sichuan Province, China.
  • 4. Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China.
  • 5. Department of Neurosurgery, West China Hospital; State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.
PMID: 37056148 DOI: 10.4103/1673-5374.369116
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.

Keywords
GPR120; GSDMD; NLRP3; TUG-891; ameliorating inflammation; endoplasmic reticulum stress; hemorrhagic stroke; neurological function; pyroptosis; unfolded protein response.
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