ArticleNeurobiology of aging2014
Zileuton restores memory impairments and reverses amyloid and tau pathology in aged Alzheimer's disease mice.
Article in Neurobiology of aging, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Exploring Novel Therapeutic Avenues: Drug Repurposing for Neurodegenerative Movement Disorders.Current drug research reviews · 2025Review
- Research Models to Study Ferroptosis's Impact in Neurodegenerative Diseases.Pharmaceutics · 2023Review
- The mechanisms of ferroptosis and its role in alzheimer's disease.Frontiers in molecular biosciences · 2022Review
- Brain-Specific Increase in Leukotriene Signaling Accompanies Chronic Neuroinflammation and Cognitive Impairment in a Model of Gulf War Illness.Frontiers in immunology · 2022Article
- Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues.Frontiers in pharmacology · 2022Review
- Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology.Molecular psychiatry · 2021Article
- 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
- Preventive and Therapeutic Strategies in Alzheimer's Disease: Focus on Oxidative Stress, Redox Metals, and Ferroptosis.Antioxidants & redox signaling · 2021Review
- Iron and Ferroptosis as Therapeutic Targets in Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- The Emerging Role of the Double-Edged Impact of Arachidonic Acid- Derived Eicosanoids in the Neuroinflammatory Background of Depression.Current neuropharmacology · 2021Review
- Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice.Pharmaceutics · 2020Article
- Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Antagonism of cysteinyl leukotrienes and their receptors as a neuroinflammatory target in Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach.Molecules (Basel, Switzerland) · 2020Article
- Recent Trends in the Management of Alzheimer's Disease: Current Therapeutic Options and Drug Repurposing Approaches.Current neuropharmacology · 2020Review
- In Vitro Evaluation and Docking Studies of 5-oxo-5International journal of molecular sciences · 2019Article
- N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation.Frontiers in pharmacology · 2019Review
- Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy.Molecular neurobiology · 2018Article
- Old Drugs as New Treatments for Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The enzyme 5-lipoxygenase (5LO) is upregulated in Alzheimer's disease (AD), and its pharmacologic blockade with zileuton slows down the development of the AD-like phenotype in young AD mice. However, its efficacy after the AD pathology is established is unknown. To this end, starting at 12 months of age triple transgenic mice (3xTg) received zileuton, a selective 5LO inhibitor, or placebo for 3 months, and then the effect of this treatment on behavior, amyloid, and tau pathology assessed. Although mice on placebo showed worsening of their memory, treated mice performed even better than at baseline. Compared with placebo, treated mice had significantly less Aβ deposits and tau phosphorylation secondary to reduced γ-secretase and CDK-5 activation, respectively. Our data provide novel insights into the disease-modifying action of pharmacologically inhibiting 5LO as a viable AD therapeutic approach. They represent the successful completion of preclinical studies for the development of this class of drug as clinically applicable therapy for the disease.
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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.