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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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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