What is it about?
Pyroptosis is a highly inflammatory type of programmed cell death occurring in response to invasive pathogens. Here, we first report that ZIKV exposure causes neural progenitor cell pyroptosis, mediated by activation of caspase-1 and gasdermin D in vivo as well as in vitro, which links ZIKV to the development and progression of microcephaly. Importantly, caspase-1 depletion or its inhibitor VX-765 treatment reduced ZIKV-induced inflammatory responses and pyroptosis, and substantially attenuated neuropathology and brain atrophy in vivo.
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Why is it important?
Zika virus (ZIKV) has been identified as a cause of microcephaly. However, the mechanisms by which ZIKV disrupts neurogenesis and causes microcephaly remains poorly understood. Our data identify caspase-1– and GSDMD-mediated pyroptosis in neural progenitor cells as a previously unrecognized mechanism for ZIKV-related pathological effects during neural development, and also provide treatment options for ZIKV-associated diseases.
Perspectives
Our study has shown that VX-765 treatment has significant and sustained beneficial effects on ZIKV-associated neuropathy and brain atrophy, so it would be particularly interesting to see whether VX-765 would be clinically effective against ZIVK-associated diseases. However, prior to clinical use, it would be necessary to carry out clinical studies of VX-765, especially of its safety profile in pregnant women, as well as for clinical efficacies against ZIKV-associated microcephaly.
Zhenjian He
Sun Yat-Sen University
Read the Original
This page is a summary of: Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target, Proceedings of the National Academy of Sciences, September 2020, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2007773117.
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