Abstract
Despite the effectiveness of combined antiretroviral therapy (cART) in suppressing virus replication, chronic inflammation remains one of the cardinal features intersecting HIV-1, cART, drug abuse, and likely contributes to the accelerated neurocognitive decline and aging in people living with HIV-1 (PLWH) that abuse drugs. It is also estimated that ~30–60% of PLWH on cART develop cognitive deficits associated with HIV-1-associated neurocognitive disorders (HAND), with symptomatology ranging from asymptomatic to mild, neurocognitive impairments. Adding further complexity to HAND is the comorbidity of drug abuse in PLWH involving activated immune responses and the release of neurotoxins, which, in turn, mediate neuroinflammation. Premature or accelerated aging is another feature of drug abusing PLWH on cART regimes. Emerging studies implicate the role of HIV-1/HIV-1 proteins, cART, and abused drugs in altering the inflammasome signaling in the central nervous system (CNS) cells. It is thus likely that exposure of these cells to HIV-1/HIV-1 proteins, cART, and/or abused drugs could have synergistic/additive effects on the activation of inflammasomes, in turn, leading to exacerbated neuroinflammation, ultimately resulting in premature aging referred to as “inflammaging” In this review, we summarize the current knowledge of inflammasome activation, neuroinflammation, and aging in central nervous system (CNS) cells such as microglia, astrocytes, and neurons in the context of HIV-1 and drug abuse.
Highlights
The advent of combined antiretroviral therapies for HIV-1 infection in the mid-1990s has been one of modern medicines most dramatic triumphant stories
In this we summarize the current knowledge of inflammasome activation, microglia, astrocytes, andreview, neurons
Thedevelopment developmentofofbrain-penetrating brain-penetrating small molecules that function and small molecules that cancan function as as scavengers, inflammasome modulators, and anti-inflammatory molecules that can reactive oxygen species (ROS) scavengers, inflammasome modulators, and anti-inflammatory molecules that can dampen dampen inflammasome signaling could be considered as potential therapeutic strategiesstrategies for restoring inflammasome signalingpathways pathways could be considered as potential therapeutic for cognitive deficits associated with neurodegenerative disorders as well as neuroinflammaging
Summary
The advent of combined antiretroviral therapies (cART) for HIV-1 infection in the mid-1990s has been one of modern medicines most dramatic triumphant stories. People with substance use disorders are less likely to adhere to the life-saving HIV-1 medication regimen [41], thereby leading to the activation of virus blips during their illness Drugs can make it easier for HIV-1 to enter the brain and trigger an immune response and initiate glial activation and release of neurotoxins, which, in turn, mediate neuroinflammation [42]. CNS such as microglia, astrocytes, and neurons It is likely exposure of cells to have effects in activation of inflammasomes, thusthat contributing tothese exacerbated and/or abused drugs can have synergistic/additive effects in activation of neuroinflammation, culminating into “inflammaging”. Neuroinflammation, and aging in CNS cells such as microglia, astrocytes, and neurons
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
