SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1α positive feedback loop

The Journal of Headache and Pain

Research

Zheman Xiao¹  Jingjing Liang¹  Man Ding¹  Shanghua Fan¹  Tao Qiu²  Lili Zhang²  Yajuan Wang²  Luyu Hu²  Zhengming Shan²  Yanjie Zhou²  Yu Zhang² 

[1] Department of Neurology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuchang District, 430060, Wuhan, Hubei Province, China;Department of Neurology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuchang District, 430060, Wuhan, Hubei Province, China;Central Laboratory, Renmin Hospital of Wuhan University, 9 Zhang Zhidong Road, Wuchang District, 430060, Wuhan, Hubei Province, China;

关键词: SS-31;    Migraine;    Mitochondrial dysfunction;    Mitochondrial homeostasis;    Sirt3;    Pgc-1α;   

DOI  :  10.1186/s10194-023-01600-6

 received in 2022-11-27, accepted in 2023-05-23,  发布年份 2023

来源: Springer

【 摘 要 】

Migraine is the second highest cause of disability worldwide, bringing a huge socioeconomic burden. Improving mitochondrial function has promise as an effective treatment strategy for migraine. Szeto-Schiller peptide (SS-31) is a new mitochondria-targeted tetrapeptide molecule that has been shown to suppress the progression of diseases by restoring mitochondrial function, including renal disease, cardiac disease, and neurodegenerative disease. However, whether SS-31 has a therapeutic effect on migraine remains unclear. The aim of this study is to clarify the treatment of SS-31 for headache and its potential mechanisms. Here we used a mouse model induced by repeated dural infusion of inflammatory soup (IS), and examined roles of Sirt3/Pgc-1α positive feedback loop in headache pathogenesis and mitochondrial function. Our results showed that repeated IS infusion impaired mitochondrial function, mitochondrial ultrastructure and mitochondrial homeostasis in the trigeminal nucleus caudalis (TNC). These IS-induced damages in TNC were reversed by SS-31. In addition, IS-induced nociceptive responses were simultaneously alleviated. The effects of SS-31 on mitochondrial function and mitochondrial homeostasis (mainly mitochondrial biogenesis) were attenuated partially by the inhibitor of Sirt3/Pgc-1α. Overexpression of Sirt3/Pgc-1α increased the protein level of each other. These results indicated that SS-31 alleviated nociceptive responses and restored mitochondrial function in an IS-induced headache mouse model via Sirt3/Pgc-1α positive feedback loop. SS-31 has the potential to be an effective drug candidate for headache treatment.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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