National Institutes of Health

Description

Neuroinflammation triggered by brain trauma, neurodegenerative diseases and neurotoxicant-induced CNS disorders initiates CNS innate immune responses that activate inflammasomes. Inflammasomes are high molecular weight complexes in the cytosol of stimulated immune cells that mediate the activation of inflammatory cascades. In response to insults, Nod-like receptors (NLRs) recruit adaptor proteins and caspase-1 to assemble inflammasomes and process the release of pro-inflammatory cytokines IL-1?, IL-18 and IL-33. Recent evidence suggests that chronic drug exposure, i.e., cocaine, methamphetamine and morphine, can induce inflammasome activation primarily mediated by NLRP3 within microglia. Additionally, emerging data suggest that HIV-1 infection can also prime inflammasome activation. Drug abuse, especially in association with HIV-1 infection, induces ROS production, impairs blood brain barrier integrity, and promotes monocyte transmigration. These upstream events exert synergistic effects that prime oligomerization and activation of inflammasome and release of pro-inflammatory cytokine IL-1?. The scientific objective of this research is to delineate the role of inflammasomes in neuropathology produced by chronic drug exposure and HIV infection. Understanding the involvement of inflammasome in the immune activation may help identify molecular markers and immune cells associated with HIV-1 disease progression among substance abuse populations, and identify novel targets for intervention to treat neuroinflammation and immune dysregulation aroused in these processes.

Who can apply

• State governments
• County governments
• City or township governments
• Special district governments
• Independent school districts
• Public and State controlled institutions of higher education
• Native American tribal governments (Federally recognized)
• Public housing authorities / Indian housing authorities
• Native American tribal organizations (other than Federally recognized)
• Nonprofits with 501(c)(3) status (other than higher education)
• Nonprofits without 501(c)(3) status (other than higher education)
• Private institutions of higher education
• For-profit organizations other than small businesses
• Small businesses
• Others

Contact

NIH OER Webmaster<br/>FBOWebmaster@OD.NIH.GOV
FBOWebmaster@OD.NIH.GOV