ArticleMolecular neurobiology2018
Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 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
13 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- 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
- Arachidonic acid metabolism in health and disease.MedComm · 2023Review
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen.Pharmaceuticals (Basel, Switzerland) · 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
- 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
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
- 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
- Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death.Oxidative medicine and cellular longevity · 2019Review
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- Novel Key Players in the Development of Tau Neuropathology: Focus on the 5-Lipoxygenase.Journal of Alzheimer's disease : JAD · 2018Review
Corrections and comments
- Retraction · 2023-02-24Duplication of/in Article · Duplication of/in Image · Unreliable Data ·
- Retracted
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Brain accumulation of increasing amount of phosphorylated microtubule associated tau protein is one the major hallmark lesions of Alzheimer's disease (AD) and related tauopathies. Consistent evidence from clinical and animal studies has shown that neuroinflammation characterizes these diseases. The 5-lipoxygenase (5LO) is an enzyme protein whose metabolic products are lipids with potent inflammatory actions. Previously, we showed that blockade of 5LO activation ameliorates the phenotype of the htau transgenic mice. Here, by employing a vector system to overexpress 5LO in the brain of the same mouse model, we investigated its role and contribution to their behavioral deficits and development of tau neuropathology. Compared with controls, 5LO gene targeted mice manifested significant impairments in their memory and learning ability. On the other hand, brain tissues of the same mice had higher 5LO protein level and activity which resulted in intense neuroinflammation and synaptic pathology. Further, the same mice had a significant elevation of tau phosphorylation, which associated with the activation of the cdk5 kinase and an accumulation of insoluble tau. The functional involvement of this kinase in the 5LO-dependent tau phosphorylation was confirmed in neuronal cells. Taken together, our findings demonstrate that neuronal 5LO is directly involved in tau phosphorylation and tau neuropathology, and for this reason, it should be considered a good therapeutic target for tauopathies.
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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.