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

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

Journal Name: Current Molecular Pharmacology

Volume 14 , Issue 4 , 2021


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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.

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

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Article Details

VOLUME: 14
ISSUE: 4
Year: 2021
Published on: 10 August, 2020
Page: [579 - 586]
Pages: 8
DOI: 10.2174/1874467213666200810140749
Price: $65

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