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RETRACTED ARTICLE: Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy

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This article was retracted on 24 February 2023

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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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Acknowledgments

This study was supported in part by a grant for the Wanda Simone Endowment for Neuroscience.

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Authors and Affiliations

  1. Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, MERB, 947, Philadelphia, PA, 19140, USA

    Phillip F. Giannopoulos & Domenico Praticò

Authors
  1. Phillip F. Giannopoulos
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  2. Domenico Praticò
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Contributions

P.F.G. and D.P. designed the study, developed the experimental design, performed data analyses, and wrote the paper. P.F.G. performed the experiments. All authors discussed the results and commented on the manuscript.

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Correspondence to Domenico Praticò.

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The authors declare that they have no conflict of interest.

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Giannopoulos, P.F., Praticò, D. RETRACTED ARTICLE: Overexpression of 5-Lipoxygenase Worsens the Phenotype of a Mouse Model of Tauopathy. Mol Neurobiol 55, 5926–5936 (2018). https://doi.org/10.1007/s12035-017-0817-7

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  • DOI: https://doi.org/10.1007/s12035-017-0817-7

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