ArticleMolecular neurodegeneration2012
Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice.
Article in Molecular neurodegeneration, 2012. 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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Who cites it
33 citing papers in PubMed, 72 citations in OpenAlex.
- Leukotriene signaling in neurodegeneration: implications for treatment strategies.Inflammopharmacology · 2024Review
- Quantitative Profiling Method for Oxylipins in Neurodegenerative Diseases by Liquid Chromatography Coupled with Tandem Mass Spectrometry.bioRxiv : the preprint server for biology · 2023Article
- Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus accumbens Preventing Amphetamine Relapse.Molecular neurobiology · 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
- Sublingual AKBA Exerts Antidepressant Effects in the Aβ-Treated Mouse Model.Biomolecules · 2021Article
- Downregulation of autophagy by 12/15Lipoxygenase worsens the phenotype of an Alzheimer's disease mouse model with plaques, tangles, and memory impairments.Molecular psychiatry · 2021Article
- Genetic Insights into Alzheimer's Disease.Annual review of pathology · 2021Review
- Novel Therapies for Parkinsonian Syndromes-Recent Progress and Future Perspectives.Frontiers in molecular neuroscience · 2021Review
- Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.Neurochemical research · 2020Review
- Binge and Subchronic Exposure to Ketamine Promote Memory Impairments and Damages in the Hippocampus and Peripheral Tissues in Rats: Gallic Acid Protective Effects.Neurotoxicity research · 2020Article
- Rodent models for Alzheimer disease.Nature reviews. Neuroscience · 2018Review
- Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy.Molecular neurobiology · 2018Article
- Brain 5-lipoxygenase over-expression worsens memory, synaptic integrity, and tau pathology in the P301S mice.Aging cell · 2018Article
- The direct role of 5-lipoxygenase on tau pathology, synaptic integrity and cognition in a mouse model of tauopathy.Translational psychiatry · 2017Article
- Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases.Mediators of inflammation · 2017Review
- The 5-Lipoxygenase as modulator of Alzheimer's γ-secretase and therapeutic target.Brain research bulletin · 2016Review
- The Lipoxygenases: Their Regulation and Implication in Alzheimer's Disease.Neurochemical research · 2016Article
- Gene Therapy Models of Alzheimer's Disease and Other Dementias.Methods in molecular biology (Clifton, N.J.) · 2016Article
- GATA1-mediated transcriptional regulation of the γ-secretase activating protein increases Aβ formation in Down syndrome.Annals of neurology · 2016Article
- Pharmacologic inhibition of 5-lipoxygenase improves memory, rescues synaptic dysfunction, and ameliorates tau pathology in a transgenic model of tauopathy.Biological psychiatry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe 5-lipoxygenase (5LO) enzymatic pathway is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD), and that its genetic absence results in a reduction of Amyloid beta (Aβ) levels in the Tg2576 mice.Here by employing an adeno-associated viral (AAV) vector system to over-express 5LO in the same mouse model, we examined its contribution to their cognitive impairments and brain AD-like amyloid pathology.
resultsOur results showed that compared with controls, 5LO-targeted gene brain over-expression in Tg2576 mice results in significant memory deficits. On the other hand, brain tissues had a significant elevation in the levels of Aβ peptides and deposition, no change in the steady state levels of amyloid-β precursor protein (APP), BACE-1 or ADAM-10, but a significant increase in PS1, nicastrin, and Pen-2, three major components of the γ-secretase complex. Additional data indicate that the transcription factor CREB was elevated and so were the mRNA levels for PS1, nicastrin and Pen-2.
conclusionsThese data demonstrate that neuronal 5LO plays a functional role in the pathogenesis of AD-like amyloidotic phenotype by modulating the γ-secretase pathway. They support the hypothesis that this enzyme is a novel therapeutic target for the treatment and prevention of AD.
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