ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2021
Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Increased Amyloidogenic Neuronal Injury in HIV-1-infected APP-KI Alzheimer's disease mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview.International journal of molecular sciences · 2026Review
- Exposure to Frontline Antiretroviral Dolutegravir Disrupts Oligodendrocyte Development Across Differentiation Stages.ASN neuro · 2026Article
- From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.Neuroscience applied · 2026Review
- Article
- Oxidative Stress in HIV-Associated Neurodegeneration: Mechanisms of Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons.International journal of molecular sciences · 2024Article
- Antiretroviral treatment reveals a novel role for lysosomes in oligodendrocyte maturation.Journal of neurochemistry · 2023Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Article
- HIV-Associated Insults Modulate ADAM10 and Its Regulator Sirtuin1 in an NMDA Receptor-Dependent Manner.Cells · 2022Article
- Endolysosome Localization of ERα Is Involved in the Protective Effect of 17α-Estradiol against HIV-1 gp120-Induced Neuronal Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Article
- Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine.Frontiers in cell and developmental biology · 2021Review
- Janus sword actions of chloroquine and hydroxychloroquine against COVID-19.Cellular signalling · 2020Article
- Role of endolysosomes and inter-organellar signaling in brain disease.Neurobiology of disease · 2020Review
- N-Acetylcysteine Reverses Antiretroviral-Mediated Microglial Activation by Attenuating Autophagy-Lysosomal Dysfunction.Frontiers in neurology · 2020Article
- The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley.Current HIV research · 2019Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Antiretroviral therapeutics (ART) have effectively increased the long-term survival of HIV-1 infected individuals. However, the prevalence of HIV-1 associated neurocognitive disorders (HAND) has increased and so too have clinical manifestations and pathological features of Alzheimer's disease (AD) in people living with HIV-1/AIDS. Although underlying mechanisms are not clear, chronic exposure to ART drugs has been implicated in the development of AD-like symptoms and pathology. ART drugs are categorized according to their mechanism of action in controlling HIV-1 levels. All ART drugs are organic compounds that can be classified as being either weak acids or weak bases, and these physicochemical properties may be of central importance to ART drug-induced AD-like pathology because weak bases accumulate in endolysosomes, weak bases can de-acidify endolysosomes where amyloidogenesis occurs, and endolysosome de-acidification increases amyloid beta (Aβ) protein production and decreases Aβ degradation. Here, we investigated the effects of ART drugs on endolysosome pH and Aβ levels in rat primary cultured neurons. ART drugs that de-acidified endolysosomes increased Aβ levels, whereas those that acidified endolysosomes decreased Aβ levels. Acidification of endolysosomes with the mucolipin transient receptor potential (TRPML) channel agonist ML-SA1 blocked ART drug-induced increases in Aβ levels. Further, ART drug-induced endolysosome de-acidification increased endolysosome sizes; effects that were blocked by ML-SA1-induced endolysosome acidification. These results suggest that ART drug-induced endolysosome de-acidification plays an important role in ART drug-induced amyloidogenesis and that endolysosome acidification might attenuate AD-like pathology in HIV-1 positive people taking ART drugs that de-acidify endolysosomes. Graphical Abstract.
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Registered trials
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