ArticlePloS one2013
Zileuton improves memory deficits, amyloid and tau pathology in a mouse model of Alzheimer's disease with plaques and tangles.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
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- Effects of molecular interactions between the exposome and oxylipin metabolism on healthspan.Frontiers in physiology · 2025Review
- Effects of APOE4 on omega-3 brain metabolism across the lifespan.Trends in endocrinology and metabolism: TEM · 2024Review
- Stress-mediated aggregation of disease-associated proteins in amyloid bodies.Scientific reports · 2023Article
- Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications.Acta pharmaceutica Sinica. B · 2022Article
- Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway.International journal of molecular sciences · 2022Article
- Leukotriene Signaling as a Target in α-Synucleinopathies.Biomolecules · 2022Review
- Interrelationship between the 5-lipoxygenase pathway and microbial dysbiosis in the progression of Alzheimer's disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice.International journal of molecular sciences · 2021Article
- The Emerging Role of the Double-Edged Impact of Arachidonic Acid- Derived Eicosanoids in the Neuroinflammatory Background of Depression.Current neuropharmacology · 2021Review
- Iron and Ferroptosis as Therapeutic Targets in Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways.Current neuropharmacology · 2021Review
- Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice.Pharmaceutics · 2020Article
- Microglia depletion diminishes key elements of the leukotriene pathway in the brain of Alzheimer's Disease mice.Acta neuropathologica communications · 2020Article
- New flavonoid -Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Learning Impairments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes Biosynthesis: Role of the cdk5 Kinase Pathway.Molecular neurobiology · 2019Article
- Novel Key Players in the Development of Tau Neuropathology: Focus on the 5-Lipoxygenase.Journal of Alzheimer's disease : JAD · 2018Review
- Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer's phenotype.Scientific reports · 2017Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
The 5-lipoxygenase (5LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD), and plays an active role in the development of brain amyloidosis in the APP transgenic mice. In the present paper, we studied the effect of its pharmacological inhibition on the entire AD-like phenotype of a mouse model with plaques and tangles, the 3 × Tg mice. Compared with mice receiving placebo, the group treated with zileuton, a specific 5LO inhibitor, manifested a significant improvement of their memory impairments. The same animals had a significant reduction in Aβ levels and deposition, which was secondary to a down-regulation of the γ-secretase pathway. Additionally, while total tau levels were unchanged for both groups, zileuton-treated mice had a significant reduction in its phosphorylation state and insoluble forms, secondary to a decreased activation of the cdk5 kinase. These data establish a functional role for 5LO in the pathogenesis of the full spectrum of the AD-like phenotype and represent the successful completion of the initial step for the preclinical development of 5LO inhibitors as viable therapeutic agents for 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.