ArticleMolecular psychiatry2021
Downregulation of autophagy by 12/15Lipoxygenase worsens the phenotype of an Alzheimer's disease mouse model with plaques, tangles, and memory impairments.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 21 citations in OpenAlex.
- 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
- Autophagy in Neuroinflammation: A Focus on Epigenetic Regulation.Aging and disease · 2024Review
- Autophagy Balances Neuroinflammation in Alzheimer's Disease.Cellular and molecular neurobiology · 2023Review
- Retraction Note to: Full recovery of the Alzheimer's disease phenotype by gain of function of vacuolar protein sorting 35.Molecular psychiatry · 2023Article
- Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential.Acta pharmaceutica Sinica. B · 2022Review
- Application of Metabolomics in the Study of Starvation-Induced Autophagy inJournal of fungi (Basel, Switzerland) · 2021Article
- Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics.Pharmacology & therapeutics · 2021Review
- Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics.Clinical and experimental pharmacology & physiology · 2021Review
- Neuroprotective effects of ZL006 in AβNeural regeneration research · 2020Article
- Alzheimer's disease: phenotypic approaches using disease models and the targeting of tau protein.Expert opinion on therapeutic targets · 2020Review
- Lanthanum Chloride Impairs Learning and Memory and Induces Dendritic Spine Abnormality by Down-Regulating Rac1/PAK Signaling Pathway in Hippocampus of Offspring Rats.Cellular and molecular neurobiology · 2020Article
- Exploring the bi-directional relationship between autophagy and Alzheimer's disease.CNS neuroscience & therapeutics · 2020Review
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Among the different initiating events in Alzheimer's disease (AD) pathogenesis, oxidative stress and neuroinflammation are some of the most iimportant. In the central nervous system, the 12/15Lipoxygenase (12/15LO) enzyme is the source of potent pro-oxidants and inflammatory lipid mediators. Previous works showed that this pathway is up-regulated in AD brains and that its pharmacological targeting modulates the phenotype of transgenic mouse models of the disease. Here we investigate the effect of brain 12/15LO gene delivery on the AD-like phenotype of a mouse model with plaques, tangles and behavioral deficits, the 3xTg mice. Compared with controls, mice over-expressing 12/15LO manifested an exacerbation of spatial learning and memory impairments, which was associated with significant increase in Aβ formation and deposition, and accumulation of hyper-phosphorylated insoluble tau secondary to a down-regulation of autophagy. In addition, the same mice manifested a worsening of neuroinflammation and synaptic pathology. Taken together our study supports the hypothesis that the 12/15LO enzymatic pathway by impairing neuronal autophagy plays a functional role in exacerbating AD-related neuropathologies and cognitive impairments. It provides further critical preclinical evidence to justify developing and testing new and selective 12/15LO inhibitors for AD treatment.
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