Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• Chronic low-grade inflammation is a hallmark of HIV-1 infection, even with combined antiretroviral therapy (cART).
• This inflammation contributes to accelerated cognitive decline and aging in HIV-1 patients, indicating limitations of cART in fully suppressing viremia.
• Drug abuse complicates cognitive defects in ~50% of HIV-1 patients on cART, activating central nervous system (CNS) cells and releasing neurotoxins, leading to neuroinflammation.

Purpose of the Study:

• To review the potential role of autophagy in the mechanism of neuroinflammaging.
• To explore the combined toxicity of HIV-1, cART, and drug abuse on CNS cells and autophagy.
• To understand how autophagy impairment contributes to neuroinflammation and accelerated aging in HIV-1-infected individuals with a history of drug abuse.

Main Methods:

• Literature review focusing on autophagy, HIV-1, drug abuse, and neuroinflammation.
• Analysis of existing evidence linking impaired autophagy to CNS cell dysfunction and immune senescence.
• Synthesis of data on the interplay between HIV-1 proteins, cART, drug abuse, and autophagy in the context of neuroinflammaging.

Main Results:

• Impaired autophagy is identified as an underlying mechanism in HIV-1-associated neurocognitive disorders (HAND), particularly in patients with co-occurring drug abuse.
• Autophagy impairment in CNS cells (neurons, microglia, astrocytes, pericytes) exposed to HIV-1, cART, and drugs can lead to combined toxicity.
• This toxicity results in increased neuroinflammation, immune senescence, and accelerated aging, termed neuroinflammaging.

Conclusions:

• Autophagy plays a critical role in maintaining CNS homeostasis and regulating cellular responses.
• Impairment of autophagy in the context of HIV-1 infection and drug abuse significantly contributes to neuroinflammation and neuroinflammaging.
• Targeting autophagy may offer a therapeutic strategy to mitigate neuroinflammation and slow cognitive decline and aging in this vulnerable population.