ArticleJournal of Alzheimer's disease : JAD2019
Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026Article
- Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative DiseasesCurrent neuropharmacology · 2025Review
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- Lysosomal CaScientific reports · 2024Article
- Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons.International journal of molecular sciences · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study.Translational psychiatry · 2023Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Lysosomal Potassium Channels.Handbook of experimental pharmacology · 2023Review
- Rethinking of Alzheimer's disease: Lysosomal overloading and dietary therapy.Frontiers in aging neuroscience · 2023Article
- Axonal transport of late endosomes and amphisomes is selectively modulated by local CaScience advances · 2022Article
- Interaction between TRPML1 and p62 in Regulating Autophagosome-Lysosome Fusion and Impeding Neuroaxonal Dystrophy in Alzheimer's Disease.Oxidative medicine and cellular longevity · 2022Article
- Role of Lysosomal Acidification Dysfunction in Mesenchymal Stem Cell Senescence.Frontiers in cell and developmental biology · 2022Review
- Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- 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
- Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases.Frontiers in physiology · 2020Review
- BK channels regulate extracellular Tat-mediated HIV-1 LTR transactivation.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Cholesterol dyshomeostasis has been linked to the pathogenesis of sporadic Alzheimer's disease (AD). In furthering the understanding of mechanisms by which increased levels of circulating cholesterol augments the risk of developing sporadic AD, others and we have reported that low-density lipoprotein (LDL) enters brain parenchyma by disrupting the blood-brain barrier and that endolysosome de-acidification plays a role in LDL-induced amyloidogenesis in neurons. Here, we tested the hypothesis that endolysosome de-acidification was central to amyloid-β (Aβ) generation and that acidifying endolysosomes protects against LDL-induced increases in Aβ levels in neurons. We demonstrated that LDL, but not HDL, de-acidified endolysosomes and increased intraneuronal and secreted levels of Aβ. ML-SA1, an agonist of endolysosome-resident TRPML1 channels, acidified endolysosomes, and TRPML1 knockdown attenuated ML-SA1-induced endolysosome acidification. ML-SA1 blocked LDL-induced increases in intraneuronal and secreted levels of Aβ as well as Aβ accumulation in endolysosomes, prevented BACE1 accumulation in endolysosomes, and decreased BACE1 activity levels. LDL downregulated TRPML1 protein levels, and TRPML1 knockdown worsens LDL-induced increases in Aβ. Our findings suggest that endolysosome acidification by activating TRPML1 may represent a protective strategy against sporadic AD.
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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.