Award
NIH Reporter #5R01DA062274-02
Molecular interplay of HIV Tat, cocaine, and cART in microglial pyroptosis: Role of NLRP3 inflammasome
Recipient
University of Nebraska Medical Center, Omaha, NE, United States
Award Amount
$448,062.00
Ceiling
$448,062.00
Awarded
January 30, 2026
Identifier
5R01DA062274-02
The award supports research investigating how HIV Tat, cocaine, and antiretroviral therapy interact to activate the NLRP3 inflammasome in microglia, leading to pyroptosis and neuroinflammation in NeuroHIV. The study aims to uncover molecular mechanisms and validate findings in vitro and in vivo, potentially identifying new therapeutic targets.
Description
This project aims to elucidate the molecular mechanisms underlying the interplay between HIV Tat, cocaine, and cART in activating NLRP3 inflammasome signaling pathways, leading to pyroptosis and microglial activation. The study will test two specific aims: 1) to determine the molecular mechanisms of NLRP3-mediated pyroptosis in microglia exposed to HIV Tat, cocaine, and cART in vitro; 2) to validate the effects of HIV Tat, cocaine, and cART on NLRP3-mediated pyroptosis and microglial activation in vivo and ex vivo using archival macaque brain tissues.