Abstract:
:The human immunodeficiency virus-1 (HIV-1) envelope protein gp120 is the major contributor to the pathogenesis of HIV-associated neurocognitive disorder (HAND). Neuroinflammation plays a pivotal role in gp120-induced neuropathology, but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown. Here, we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy. Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1β production in microglia. Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury. Importantly, we showed that chronic administration of MCC950, a novel selective NLRP3 inhibitor, to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function. In conclusion, our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND.
journal_name
Cell Mol Immunoljournal_title
Cellular & molecular immunologyauthors
He X,Yang W,Zeng Z,Wei Y,Gao J,Zhang B,Li L,Liu L,Wan Y,Zeng Q,Gong Z,Liu L,Zhang H,Li Y,Yang S,Hu T,Wu L,Masliah E,Huang S,Cao Hdoi
10.1038/s41423-019-0260-ysubject
Has Abstractpub_date
2020-03-01 00:00:00pages
283-299issue
3eissn
1672-7681issn
2042-0226pii
10.1038/s41423-019-0260-yjournal_volume
17pub_type
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