ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Activation of TRPML1 clears intraneuronal Aβ in preclinical models of HIV infection.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 105 citations in OpenAlex.
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- HIV Tat-activated microglial extracellular vesicles induce neuronal iron dysregulation and synaptodendritic injury.Cell communication and signaling : CCS · 2026Article
- Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity.Redox report : communications in free radical research · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- HIF-1 Targeting Intervention Renders Protection From Alzheimer's-Like Pathology in a Humanized Mice Model of HIV Infection.Journal of extracellular vesicles · 2025Article
- Transient receptor potential channels in viral infectious diseases: Biological characteristics and regulatory mechanisms.Journal of advanced research · 2025Review
- Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative DiseasesCurrent neuropharmacology · 2025Review
- Integrated transcriptomic and single-cell RNA sequencing identifies lysosomal ion channel genes as potential biomarkers for Alzheimer's disease.Frontiers in genetics · 2025Article
- TRPML1 activation ameliorates lysosomal phenotypes in CLN3 deficient retinal pigment epithelial cells.Scientific reports · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Quantitative Proteomic and Phosphoproteomic Analyses Reveal a Role of Death-Associated Protein Kinase 1 in Regulating Hippocampal Synapse.Molecular neurobiology · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice.Pharmaceutical research · 2023Article
- Increased expression or activation of TRPML1 reduces hepatic storage of toxic Z alpha-1 antitrypsin.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Antiretroviral treatment reveals a novel role for lysosomes in oligodendrocyte maturation.Journal of neurochemistry · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Antiretroviral therapy extends the lifespan of human immunodeficiency virus (HIV)-infected patients, but many survivors develop premature impairments in cognition. These residual cognitive impairments may involve aberrant deposition of amyloid β-peptides (Aβ). By unknown mechanisms, Aβ accumulates in the lysosomal and autophagic compartments of neurons in the HIV-infected brain. Here we identify the molecular events evoked by the HIV coat protein gp120 that facilitate the intraneuronal accumulation of Aβ. We created a triple transgenic gp120/APP/PS1 mouse that recapitulates intraneuronal deposition of Aβ in a manner reminiscent of the HIV-infected brain. In cultured neurons, we found that the HIV coat protein gp120 increased the transcriptional expression of BACE1 through repression of PPARγ, and increased APP expression by promoting interaction of the translation-activating RBP heterogeneous nuclear ribonucleoprotein C with APP mRNA. APP and BACE1 were colocalized into stabilized membrane microdomains, where the β-cleavage of APP and Aβ formation were enhanced. Aβ-peptides became localized to lysosomes that were engorged with sphingomyelin and calcium. Stimulating calcium efflux from lysosomes with a TRPM1 agonist promoted calcium efflux, luminal acidification, and cleared both sphingomyelin and Aβ from lysosomes. These findings suggest that therapeutics targeted to reduce lysosomal pH in neurodegenerative conditions may protect neurons by facilitating the clearance of accumulated sphingolipids and Aβ-peptides.
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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.