ArticleThe American journal of pathology2017
HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via β-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- HIF-1 Targeting Intervention Renders Protection From Alzheimer's-Like Pathology in a Humanized Mice Model of HIV Infection.Journal of extracellular vesicles · 2025Article
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- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Genetic knock-in of EIF2AK3 variants reveals differences in PERK activity in mouse liver and pancreas under endoplasmic reticulum stress.Scientific reports · 2024Article
- Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- Update on Central Nervous System Effects of HIV in Adolescents and Young Adults.Current HIV/AIDS reports · 2023Review
- HIV-Associated Insults Modulate ADAM10 and Its Regulator Sirtuin1 in an NMDA Receptor-Dependent Manner.Cells · 2022Article
- Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV.AIDS research and human retroviruses · 2022Article
- CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice.Molecular neurodegeneration · 2021Article
- Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae.Viruses · 2021Review
- Protease Inhibitors, Saquinavir and Darunavir, Inhibit Oligodendrocyte Maturation: Implications for Lysosomal Stress.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Article
- Antiretroviral Drugs Regulate Epigenetic Modification of Cardiac Cells Through Modulation of H3K9 and H3K27 Acetylation.Frontiers in cardiovascular medicine · 2021Article
- Effect of green tea consumption in treatment of mild to moderate depression in Iranian patients living with HIV: A double-blind randomized clinical trial.Chinese herbal medicines · 2021Article
- A candidate gene study of intermediate histopathological phenotypes in HIV-associated neurocognitive disorders.Journal of neurovirology · 2020Article
- The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration.Journal of neuropathology and experimental neurology · 2020Review
- White matter loss and oligodendrocyte dysfunction in HIV: A consequence of the infection, the antiretroviral therapy or both?Brain research · 2019Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of β-site APP cleaving enzyme-1 (BACE1). In addition, PIs induced β-amyloid production, indicative of increased BACE1-mediated APP processing, in rodent neuroglial cultures and human APP-expressing Chinese hamster ovary cells. Inhibition of BACE1 activity protected against neuronal damage. Finally, ARVs administered to mice and SIV-infected macaques resulted in neuronal damage and BACE1 up-regulation in the central nervous system. These findings implicate a subset of PIs as potential mediators of neurodegeneration in HIV-associated neurocognitive disorders.
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