Co-activation of Caspase-1 and Caspase-8 in CMV-induced SGN death by inflammasome-associated pyroptosis and apoptosis

在 CMV 诱导的 SGN 死亡中,Caspase-1 和 Caspase-8 通过炎症小体相关的细胞焦亡和凋亡共同激活

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作者:Menghua Li, Liyuan Wu, Mengbing Chen, Yanfen Dong, Liting Zheng, Daishi Chen, Yuehua Qiao, Zhaoyang Ke, Xi Shi

Abstract

Cytomegalovirus (CMV) infection causes newborn deafness, and the death of the spiral ganglion neurons (SGNs) is crucial in determining the degree of CMV-related hearing loss. Therefore, understanding the psychopathology of CMV-related SGN loss is important for identifying targets and exploring treatment strategies. In this study, we found that pyroptosis and apoptosis, two inflammasome-related programmed cell death pathways, are involved in CMV-induced SGN death and are mainly regulated by activated caspase-1 and caspase-8. Moreover, suppressing inflammasome assembly by blocking apoptosis-associated speck-like protein containing a CARD (ASC) interaction inhibited the activation of both caspase-1 and caspase-8, rescued SGN death, and improved hearing loss in CMV-infected newborn mice. Therefore, we propose that ASC inflammasome might be a promising target for treating CMV-related SGN death and newborn hearing loss by inhibiting caspase-1 and caspase-8 activated pyroptosis and apoptosis.

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