Molecular Mechanism of a Specific NLRP3 Inhibitor to Alleviate Seizure Severity Induced by Pentylenetetrazole

Title:Molecular Mechanism of a Specific NLRP3 Inhibitor to Alleviate Seizure Severity Induced by Pentylenetetrazole

Volume: 14

Author(s): Kai Shen, Wanzhi Jiang, Chunyan Zhang, Liangliang Cai, Qin Wang, Haiyan Yu, Zhiyuan Tang, Zhifeng Gu*Bohua Chen*

Affiliation:

• Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong,China

• Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong,China

Keywords: Epilepsy, NLRP3 inflammasome, CY-09, inflammation, apoptosis, neuron.

Abstract:

Background: While our previous research has demonstrated that the NLRP3 inflammasome is involved in epilepsy progression, the effects of the specific NLRP3 inhibitor CY-09 remain poorly understood. Therefore, the aim of the present study was to investigate the efficacy of CY-09 against pentylenetetrazole (PTZ)-induced neuronal loss in mice.

Methods: The expressions of the proinflammatory factors interleukin-1β and interleukin-18 were examined by western blot and enzyme-linked immunosorbent assays. Western blot analysis was applied to detect the level of astrocyte activation. Neuronal apoptosis was determined by western blot analysis combined with immunostaining specific for neuronal nuclei.

Results: We found that CY-09 ameliorated the progression of the kindling process and inhibited PTZ-induced neuronal loss by attenuating the activation of astrocytes and the secretion of NLRP3- dependent neuroinflammation.

Conclumsion: These findings indicate that CY-09 may represent an important treatment agent for epilepsy and other NLRP3 inflammasome-associated diseases.

Cite this article as:

Shen Kai , Jiang Wanzhi , Zhang Chunyan , Cai Liangliang , Wang Qin , Yu Haiyan , Tang Zhiyuan , Gu Zhifeng*, Chen Bohua *, Molecular Mechanism of a Specific NLRP3 Inhibitor to Alleviate Seizure Severity Induced by Pentylenetetrazole, Current Molecular Pharmacology 2021; 14 (4) . https://dx.doi.org/10.2174/1874467213666200810140749