ArticleMolecular psychiatry2015
Pharmacologic blockade of 12/15-lipoxygenase ameliorates memory deficits, Aβ and tau neuropathology in the triple-transgenic mice.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Crafting Molecular Tools for 15-Lipoxygenase-1 in a Single Step.Angewandte Chemie (International ed. in English) · 2025Article
- Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored inAntioxidants (Basel, Switzerland) · 2025Review
- 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
- Neurochemical Research of LOXBlock-1 and ZnSOBiological trace element research · 2024Article
- Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.Sleep and biological rhythms · 2023Article
- A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes.Nature communications · 2022Article
- 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
- Iron and Ferroptosis as Therapeutic Targets in Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019Article
- Oxidative Stress in the Male Germline: A Review of Novel Strategies to Reduce 4-Hydroxynonenal Production.Antioxidants (Basel, Switzerland) · 2018Review
- Tau-based therapies in neurodegeneration: opportunities and challenges.Nature reviews. Drug discovery · 2017Review
- Article
- Review
- Mice deficient in L-12/15 lipoxygenase show increased vulnerability to 3-nitropropionic acid neurotoxicity.Neuroscience letters · 2017Article
- Design of a novel thiophene inhibitor of 15-lipoxygenase-1 with both anti-inflammatory and neuroprotective properties.European journal of medicinal chemistry · 2016Article
- Activity-Based Probes for 15-Lipoxygenase-1.Angewandte Chemie (International ed. in English) · 2016Article
- Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer's Disease.Molecular neurobiology · 2016Article
- The Lipoxygenases: Their Regulation and Implication in Alzheimer's Disease.Neurochemical research · 2016Article
- The 12/15-lipoxygenase as an emerging therapeutic target for Alzheimer's disease.Trends in pharmacological sciences · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 12/15-lipoxygenase (12/15LO) enzyme is widely distributed within the central nervous system. Previous work showed that this protein is upregulated in Alzheimer's disease (AD), and plays an active role in the development of brain amyloidosis in amyloid beta (Aβ)-precursor protein transgenic mice (Tg2576). In the present paper, we studied the effect of its pharmacologic inhibition on the AD-like phenotype of a mouse model with plaques and tangles, the triple-transgenic mice. Compared with mice receiving placebo, the group treated with PD146176, a specific 12/15LO inhibitor, manifested a significant improvement of their memory deficits. The same animals had a significant reduction in Aβ levels and deposition, which was secondary to a decrease in the β-secretase pathway. In addition, while total tau-soluble levels were unchanged for both groups, PD146176-treated mice had a significant reduction in its phosphorylation state and insoluble fraction, which specifically associated with decrease in stress-activated protein kinase/c-Jun N-terminal kinase activity. In vitro study showed that the effect on tau and Aβ were independent from each other. These data establish a functional role for 12/15LO 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 12/15LO inhibitors as novel therapeutic agents for AD.
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