Year: 2025
Type: article
Abstract: While antiretroviral therapy (ART) has significantly improved the morbidity of HIV infection, ART may contribute to the pathogenesis of HIV associated neurocognitive impairment (HIV-NCI) by interfering with autophagic processes in astrocytes. Autophagy and mitophagy remove unwanted/damaged material and mitochondria from the intracellular environment, respectively. Dysregulated autophagy in astrocytes, abundant CNS cells with crucial homeostatic functions, contributes to many neurodegenerative diseases. Few studies have examined effects of ART on autophagy in astrocytes. We treated primary human astrocytes with a common ART regimen and performed LC3B-II and p62 turnover assays. ART significantly inhibited both LC3B-II and p62 turnover. Since p62, one autophagy receptor that mediates mitophagy, autophagic clearance of mitochondria, turnover was inhibited, we also examined mitophagy. While ART decreased BNIP3L/Nix homodimers, there were no changes in PINK1, Parkin, Mt-CO2, mitochondrial mass, or mitochondria-lysosome colocalization, indicating that ART did not inhibit mitophagy. We show that antiretroviral drugs have distinct effects on autophagic processes in astrocytes, which represents an alteration in their homeostasis, a major function of autophagy. This likely contributes to HIV-NCI. Understanding these impacts is important for improving ART for PWH, who have, by necessity, ongoing ART exposure. It also facilitates development of therapies for HIV-NCI that may include modulation of autophagy.
Source: Cells
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,258
Funders: National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1557182087, G2745100336, Mechanisms of opioid- mediated HIV neuropathogenesis, Monocyte CNS HIV entry & neurodegeneration: Translational studies in the CART era, Advanced Point-scanning Confocal Microscope for a Microscopy Core Facility, Impact of illicit drugs, HIV, and ART on neuroinflammation and BBB disruption, The impact of methamphetamine on CXCL12 mediated HIV neuropathogenesis, Antiretroviral Therapy Impacts Autophagy in Astrocytes, and May Contribute to HIV Associated Neurocognitive Disorders, Cancer Center Support Grant, Inflammation, BBB disruption, and Reward Function in the Pathogenesis of Depression among PWH, SUPPORT FOR THE ROSE F KENNEDY IDDRC P50, Effect of buprenorphine on monocytes in the context of neuroAids and opioid abuse
OpenAlex ID: W4416912064