2. Academic Validation
  3. Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target

Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target

  • Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23869-23878. doi: 10.1073/pnas.2007773117.
Zhenjian He 1 2,  Shu An 2 3,  Jiahui Chen 4 5,  Shuqing Zhang 2 3,  Chahui Tan 2 3,  Jianchen Yu 2 3,  Hengming Ye 1 2,  Yun Wu 2 3,  Jie Yuan 2 5 6,  Jueheng Wu 2 3,  Xun Zhu 7 3,  Mengfeng Li 7 3 8
Affiliations

Affiliations

  • 1 School of Public Health, Sun Yat-Sen University, 510080 Guangzhou, China.
  • 2 Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, 510080 Guangzhou, China.
  • 3 Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 510080 Guangzhou, China.
  • 4 Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, China.
  • 5 Innovation Platform for Public Health of Guangdong Province, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, China.
  • 6 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
  • 7 Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, 510080 Guangzhou, China; limf@mail.sysu.edu.cn zhuxun8@mail.sysu.edu.cn.
  • 8 Cancer Institute, Southern Medical University, 510515 Guangzhou, China.
PMID: 32907937 DOI: 10.1073/pnas.2007773117
Abstract

Mounting evidence has associated Zika virus (ZIKV) Infection with congenital malformations, including microcephaly, which raises global alarm. Nonetheless, mechanisms by which ZIKV disrupts neurogenesis and causes microcephaly are far from being understood. In this study, we discovered direct effects of ZIKV on neural progenitor cell development by inducing caspase-1- and gasdermin D (GSDMD)-mediated pyroptotic cell death, linking ZIKV Infection with the development 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. Collectively, 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.

Keywords

Zika virus; caspase-1; microcephaly; neurogenesis; pyroptosis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12466
    ≥98.0%, Caspase-3抑制剂
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