AZD8055 ameliorates experimental autoimmune encephalomyelitis via the mTOR/ROS/NLRP3 pathway

• Published in: Biochemical and biophysical research communications Vol. 573; pp. 27 - 34
• Main Authors: He, Miao, Wu, Dong-Ming, Zhao, Yang-Yang, Yu, Ye, Deng, Shi-Hua, Liu, Teng, Zhang, Ting, Li, Jing, Wang, Feng, Xu, Ying
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 08.10.2021
• Subjects: Autophagy; Experimental autoimmune encephalomyelitis; mTOR/ROS/NLRP3; Pyroptosis; PBS; Pyroptosis; IHC; MS; IFC; Experimental autoimmune encephalomyelitis; EAE; CNS; LFB; Autophagy; MOG35-55; mTOR/ROS/NLRP3; PTX; mTOR; AMPK; NLRP3; MBP; HE; RT-qPCR; ATG5; ELISA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.08.010

Experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), is characterized by immune-mediated demyelination and neurodegeneration. NOD-like receptor protein 3 (NLRP3) inflammasome activation aggravates spinal cord inflammation in EAE. Autophagy is associated with alleviation of systemic inflammation, including that encountered in EAE. However, the effects of autophagy on NLRP3 in EAE are still unclear. Here, we evaluated the effects of the autophagy activator AZD8055 on EAE. EAE model mice were established, histological examination was performed to assess the degree of inflammatory cell infiltration and demyelination. And the levels of autophagy and NLRP3-mediated pyroptosis in spinal cords were assessed. Western blotting and immunofluorescence analyses were performed to evaluate protein expression and localization. AZD8055 significantly enhanced autophagy in the spinal cords of EAE model mice, coupled with decreased abnormal clinical behavior scores and increased body weights. The degree of inflammatory cell infiltration and demyelination was mild in AZD8055-treated EAE model mice.Meanwhile, the pathway of ROS/NLRP3 was downregulated, and LC3 and NLRP3 were colocalized. AZD8055 ameliorated EAE through anti-inflammatory and anti-pyroptosis effects via the mammalian target of mTOR/ROS/NLRP3 pathway. These findings provide insights into the interactions between autophagy and pyroptosis and may facilitate the development of novel treatments for MS. •Experimental autoimmune encephalomyelitis (EAE) is a mouse model of MS.•The effects of the autophagy activator AZD8055 on EAE were evaluated.•AZD8055 significantly enhanced autophagy in the spinal cords of EAE model mice.•AZD8055 ameliorated EAE through anti-inflammatory and anti-pyroptosis effects.•Autophagy and pyroptosis may have an interaction via mTOR/ROS/NLRP3 pathway.