ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2012
The effect of HIV protease inhibitors on amyloid-β peptide degradation and synthesis in human cells and Alzheimer's disease animal model.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Common miRNAs, Genes, and Regulatory Pathways in Alzheimer's Disease and Type 2 Diabetes Mellitus: An Integrative Analysis of Systematic Reviews, Bioinformatics and Data Mining.Journal of neurochemistry · 2025Pooled it
- Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.Current neuropharmacology · 2019Pooled it
- CASTER-DTA: Equivariant Graph Neural Networks for Predicting Drug-Target Affinity.bioRxiv : the preprint server for biology · 2025Article
- CASTER-DTA: equivariant graph neural networks for predicting drug-target affinity.Briefings in bioinformatics · 2025Article
- From Lab to Clinic: Success Stories of Repurposed Drugs in Treating Major Diseases.Advances in pharmacological and pharmaceutical sciences · 2025Review
- The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View.Journal of clinical medicine · 2024Review
- Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKT Signaling Pathway.Toxics · 2024Article
- Reproductive toxicity of ritonavir in male: Insight into mouse sperm capacitation.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer's Disease: From In Silico to In Vivo.International journal of molecular sciences · 2022Article
- Article
- Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes.Frontiers in cardiovascular medicine · 2022Article
- Evaluation of Virtual Screening Strategies for the Identification of γ-Secretase Inhibitors and Modulators.Molecules (Basel, Switzerland) · 2021Article
- CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice.Molecular neurodegeneration · 2021Article
- Potential Roles of Sestrin2 in Alzheimer's Disease: Antioxidation, Autophagy Promotion, and Beyond.Biomedicines · 2021Review
- Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Beta amyloid levels in cerebrospinal fluid of HIV-infected people vary by exposure to antiretroviral therapy.AIDS (London, England) · 2020Article
- Blood amyloid-β protein isoforms are affected by HIV-1 in a subtype-dependent pattern.Journal of neurovirology · 2020Article
- Differential Contribution of HIV-1 Subtypes B and C to Neurological Disorders: Mechanisms and Possible Treatments.AIDS reviews · 2019Review
- Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics.International journal of molecular sciences · 2018Review
- Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C.Journal of neurovirology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Combined antiretroviral therapy (ART) tremendously improved the lifespan and symptoms associated with AIDS-defining illness in affected individuals. However, chronic ART-treated patients frequently develop age-dependent complications, including dementia, diabetes, and hyperlipidemia: all risk factors of Alzheimer's disease. Importantly, the effect of ART compounds on amyloid generation and clearance has never been systematically examined. Nine prescribed HIV protease inhibitors were tested for their effect on amyloid-β peptide (Aβ) clearance in primary cultured human monocyte-derived macrophages. Atazanavir, ritonavir, and saquinavir modestly inhibited of Aβ degradation, while lopinavir, nelfinavir, and ritonavir enhanced secretion of undigested Aβ after phagocytosis. Lopinavir, nelfinavir, ritonavir, and saquinavir inhibited endogenous Aβ40 production from primary cultured human cortical neurons, which were associated with reduction in Beta-site APP Converting Enzyme 1 (BACE1) and γ-secretase enzyme activities. However, ART compounds showed little inhibition of purified BACE1 activity in vitro, suggesting the indirect effect of ART compounds on BACE1 activity in neurons. Finally, nefinavir or lopinavir/ritonavir (Kaletra) were orally administered for 30 days into APP SCID mice expressing a double mutant form of APP 695 (KM670/671NL + V717F) in homozygosity for the scid allele of Prkdc. There was no difference in beta-amyloidosis by ART drug administration as determined by both immunohistochemistry and ELISA measurements although the therapeutic doses of the ART compounds was present in the brain. These data demonstrated that ART drugs can inhibit Aβ clearance in macrophages and Aβ production in neurons, but these effects did not significantly alter Aβ accumulation in the mouse brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.