The National Institute on Drug Abuse (NIDA) awarded a 5-year, $758,730 Project Grant (CFDA 93.279 - Drug Use and Addiction Research Programs) to the Icahn School of Medicine at Mount Sinai (ISMMS) to investigate the impact of nicotine exposure on NLRP3 inflammasome activation in the central nervous system of people living with HIV-1 and substance use disorders. The research aims to elucidate the mechanisms underlying neuroinflammation and cognitive decline in this population, with the goal of identifying potential therapeutic targets. The project will utilize human tonsil explants, iPSC-derived microglia, and a xenograft humanized mouse model to track inflammasome differential expression and activation, as well as analyze post-mortem brain samples to compare NLRP3 inflammasome markers in smokers versus non-smokers with HIV-1. By advancing the understanding of inflammation and immune response to HIV-1 in smokers, this research seeks to develop novel treatments for cognitive decline and immune dysregulation in this population.
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