ArticleProceedings of the National Academy of Sciences of the United States of America2020
Pyridoxal kinase inhibition by artemisinins down-regulates inhibitory neurotransmission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- Nervonic acid confers neuroprotection in a zebrafish model of diabetic neuropathy by promoting myelin repair and metabolic modulation.Frontiers in pharmacology · 2026Article
- Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation.Genes & development · 2025Review
- Toxic Effects of Excess Vitamins A, B6, and Folic Acid on the Nervous System.Behavioural neurology · 2025Review
- 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
- Scientific opinion on the tolerable upper intake level for vitamin B6.EFSA journal. European Food Safety Authority · 2023Article
- Loss of Extrasynaptic Inhibitory Glycine Receptors in the Hippocampus of an AD Mouse Model Is Restored by Treatment with Artesunate.International journal of molecular sciences · 2023Article
- Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response.Communications biology · 2022Article
- Artesunate Therapy Alleviates Fracture-Associated Chronic Pain After Orthopedic Surgery by Suppressing CCL21-Dependent TREM2/DAP12 Inflammatory Signaling in Mice.Frontiers in pharmacology · 2022Article
- Targeting Nutrient Dependency in Cancer Treatment.Frontiers in oncology · 2022Review
- Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity.Advances in nutrition (Bethesda, Md.) · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The antimalarial artemisinins have also been implicated in the regulation of various cellular pathways including immunomodulation of cancers and regulation of pancreatic cell signaling in mammals. Despite their widespread application, the cellular specificities and molecular mechanisms of target recognition by artemisinins remain poorly characterized. We recently demonstrated how these drugs modulate inhibitory postsynaptic signaling by direct binding to the postsynaptic scaffolding protein gephyrin. Here, we report the crystal structure of the central metabolic enzyme pyridoxal kinase (PDXK), which catalyzes the production of the active form of vitamin B6 (also known as pyridoxal 5'-phosphate [PLP]), in complex with artesunate at 2.4-Å resolution. Partially overlapping binding of artemisinins with the substrate pyridoxal inhibits PLP biosynthesis as demonstrated by kinetic measurements. Electrophysiological recordings from hippocampal slices and activity measurements of glutamic acid decarboxylase (GAD), a PLP-dependent enzyme synthesizing the neurotransmitter γ-aminobutyric acid (GABA), define how artemisinins also interfere presynaptically with GABAergic signaling. Our data provide a comprehensive picture of artemisinin-induced effects on inhibitory signaling in the brain.
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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.