ArticleMolecular neurodegeneration2023
Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Intranasal Artesunate Ameliorates Hippocampal LFP Abnormalities and Cellular Apoptosis in APP/PS1 Mice via a Mechanism Involving GHRH/PI3K/AKT Signaling.Molecular neurobiology · 2026Article
- Blood-brain barrier-penetrant nanotherapy inhibits haem oxygenase-1-mediated ferroptosis for post-resuscitation neuroprotection.Nature communications · 2026Article
- Ferroptosis-associated immune modulation enhances temozolomide efficacy in experimental glioblastoma: potential implications for T-cell infiltration and tumour microenvironment dynamics.Clinical and experimental medicine · 2026Article
- Artesunate nanoliposomes in hepatocellular carcinoma: mechanistic ferroptosis induction and translational opportunities.Discover oncology · 2026Review
- Targeting Liquid-Liquid Phase Separation and Autophagy in Alzheimer's Disease: Insights into Molecular Mechanisms and Therapeutic Potential.Neurochemical research · 2025Review
- The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Artemisinin inhibits neuronal ferroptosis in Alzheimer's disease models by targeting KEAP1.Acta pharmacologica Sinica · 2025Article
- Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro.Molecules (Basel, Switzerland) · 2025Article
- Insights into targeted ferroptosis in mechanisms, biology, and role of Alzheimer's disease: an update.Frontiers in aging neuroscience · 2025Review
- Repurposing Artemisinin-Based Drugs from Antimalarial to Pan-Therapeutic: Pharmacological Promise and Therapeutic Challenges.Drug design, development and therapy · 2025Review
- An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.iScience · 2024Article
- Another Use for a Proven Drug: Experimental Evidence for the Potential of Artemisinin and Its Derivatives to Treat Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease.Nature communications · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Endothelial Cells Are Heterogeneous in Different Brain Regions and Are Dramatically Altered in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Correction: Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.Molecular neurodegeneration · 2023Article
- Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential.Frontiers in aging neuroscience · 2023Review
- Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?Frontiers in pharmacology · 2023Review
- Blood-brain barrier endothelial cells in neurodegenerative diseases: Signals from the "barrier".Frontiers in neuroscience · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPICALM is one of the most significant susceptibility factors for Alzheimer's disease (AD). In humans and mice, PICALM is highly expressed in brain endothelium. PICALM endothelial levels are reduced in AD brains. PICALM controls several steps in Aβ transcytosis across the blood-brain barrier (BBB). Its loss from brain endothelium in mice diminishes Aβ clearance at the BBB, which worsens Aβ pathology, but is reversible by endothelial PICALM re-expression. Thus, increasing PICALM at the BBB holds potential to slow down development of Aβ pathology.
methodsTo identify a drug that could increase PICALM expression, we screened a library of 2007 FDA-approved drugs in HEK293t cells expressing luciferase driven by a human PICALM promoter, followed by a secondary mRNA screen in human Eahy926 endothelial cell line. In vivo studies with the lead hit were carried out in Picalm-deficient (Picalm
resultsOur screen identified anti-malaria drug artesunate as the lead hit. Artesunate elevated PICALM mRNA and protein levels in Eahy926 endothelial cells and in vivo in brain capillaries of Picalm
conclusionsArtesunate increases PICALM levels and Aβ clearance at the BBB which prevents development of Aβ pathology and functional deficits in mice and holds potential for translation to human AD.
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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.