Role of inflammasomes in HIV-1 and drug abuse-mediated neuroinflammation

Neuroinflammation, a critical process within the central nervous system (CNS) characterized by the activation of immune cells, has been implicated in the pathogenesis of various neurological disorders. This chapter explores the role of inflammasomes, multiprotein complexes regulating proinflammatory cytokine expression and programmed cell death, in neuroinflammation. Inflammasomes are activated by pathogen- or damage-associated molecular patterns, categorized as noncanonical or canonical, and contribute to the production of proinflammatory cytokines and pyroptotic cell death. Notably, HIV-1 infection and drug use disorder trigger inflammasome activation and chronic neuroinflammation. HIV-1-infected glial cells release viral proteins and toxins, while chronic drug use, particularly opioids, cocaine, and methamphetamine, induces neuroinflammation and inflammasome activation. This chapter also discusses the role of extracellular vesicles (EVs) in propagating neuroinflammation, highlighting their involvement in intercellular communication. Targeting inflammasome activation and regulation in CNS cells and EVs presents a promising therapeutic approach for inflammation-related neurological disorders associated with drug use and HIV-1 infection. Understanding the intricate mechanisms of inflammasome activation and regulation in CNS cells and their impact on neuroinflammation is essential for developing targeted therapies for neurological disorders, including NeuroHIV and drug use disorder.