ArticleAging cell2018
Brain 5-lipoxygenase over-expression worsens memory, synaptic integrity, and tau pathology in the P301S mice.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Anti-Inflammatory Peptide Prevents AβCells · 2025Article
- A Study of Sex Differences in the Biological Pathways of Stress Regulation in Mice.CNS neuroscience & therapeutics · 2025Article
- Leukotriene signaling in neurodegeneration: implications for treatment strategies.Inflammopharmacology · 2024Review
- Retraction Note to: Learning Impairments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes Biosynthesis: Role of the cdk5 Kinase Pathway.Molecular neurobiology · 2024Article
- CRISPR/Cas9-mediated neuronal deletion of 5-lipoxygenase alleviates deficits in mouse models of epilepsy.Journal of advanced research · 2024Article
- Effects of APOE4 on omega-3 brain metabolism across the lifespan.Trends in endocrinology and metabolism: TEM · 2024Review
- Arachidonic acid metabolism in health and disease.MedComm · 2023Review
- Proteasomal Stimulation by MK886 and Its Derivatives Can Rescue Tau-Induced Neurite Pathology.Molecular neurobiology · 2023Article
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer's Disease and Parkinson's Disease.Aging and disease · 2023Review
- Retraction Note to: Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy.Molecular neurobiology · 2023Article
- Leukotriene signaling as molecular correlate for cognitive heterogeneity in aging: an exploratory study.Frontiers in aging neuroscience · 2023Article
- Reelin changes hippocampal learning in aging and Alzheimer's disease.Behavioural brain research · 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
- RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation.Cell death and differentiation · 2021Article
- Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.Neurochemical research · 2020Review
- The Chemical Biology of Ferroptosis in the Central Nervous System.Cell chemical biology · 2020Review
- Tau inhibits PKA by nuclear proteasome-dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation.Aging cell · 2020Article
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5-lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro-inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice. By employing an adeno-associated viral vector system to over-express 5LO in the brain, we examined its contribution to the behavioral deficits and neuropathology in a different transgenic mouse model of tauopathy, the P301S mouse line. Compared with controls, 5LO-targeted gene brain over-expression in these mice resulted in a worsening of behavioral and motor deficits. Over-expression of 5LO resulted in microglia and astrocyte activation and significant synaptic pathology, which was associated with a significant elevation of tau phosphorylation at specific epitopes, tau insoluble fraction, and activation of the cdk5 kinase. In vitro studies confirmed that 5LO directly modulates tau phosphorylation at the same epitopes via the cdk5 kinase pathway. These data demonstrate that 5LO plays a direct role in tau phosphorylation and is an active player in the development of the entire tau phenotype. They provide further support to the hypothesis that 5LO is a viable therapeutic target for the treatment and/or prevention of human tauopathy.
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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.