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Minocycline and St. John’s Wort as Therapeutic Drugs for Human Tauopathy

  • Kenji Hashimoto
    Correspondence
    Address correspondence to Kenji Hashimoto, Ph.D., Division of Clinical Neuroscience, Center for Forensic Mental Health, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan
    Affiliations
    Division of Clinical Neuroscience, Center for Forensic Mental Health, Chiba UniversityChiba, Japan.
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      I read with great interest the article by Giannopoulos et al. (
      • Giannopoulos P.F.
      • Chu J.
      • Sperow M.
      • Li J.G.
      • Yu W.H.
      • Kirby L.G.
      • et al.
      Pharmacologic inhibition of 5-lipoxygenase improves memory, rescues synaptic dysfunction, and ameliorates tau pathology in a transgenic model of tauopathy.
      ) on the role of arachidonate 5-lipoxygenase (5-LO), an inflammatory enzyme, in tau pathology. Levels of 5-LO protein in the frontal cortex of patients with tauopathy and progressive supranuclear palsy were significantly higher than levels of control subjects. Compared with wild-type mice, brain cortices from transgenic tau mice showed an age-dependent increase in 5-LO levels, which reached statistical significance by 10 months of age. In contrast, there were no significant differences in the cerebellum between transgenic tau mice and wild-type mice at any of the matched time points, indicating an age-dependent and region-specific increase of 5-LO in the brains of transgenic tau mice (
      • Giannopoulos P.F.
      • Chu J.
      • Sperow M.
      • Li J.G.
      • Yu W.H.
      • Kirby L.G.
      • et al.
      Pharmacologic inhibition of 5-lipoxygenase improves memory, rescues synaptic dysfunction, and ameliorates tau pathology in a transgenic model of tauopathy.
      ). Treatment with zileuton (200 mg/L in drinking water), a selective 5-LO inhibitor, from 3 months to 10 months of age resulted in significant memory improvement, rescue of synaptic integrity and dysfunction, and a reduction of tau pathology via a cyclin-dependent kinase 5–dependent mechanism (
      • Giannopoulos P.F.
      • Chu J.
      • Sperow M.
      • Li J.G.
      • Yu W.H.
      • Kirby L.G.
      • et al.
      Pharmacologic inhibition of 5-lipoxygenase improves memory, rescues synaptic dysfunction, and ameliorates tau pathology in a transgenic model of tauopathy.
      ). These data imply that 5-LO is crucial to development of the tau pathology phenotype and highlight 5-LO inhibitors as novel therapeutic drugs for human tauopathy (
      • Giannopoulos P.F.
      • Chu J.
      • Sperow M.
      • Li J.G.
      • Yu W.H.
      • Kirby L.G.
      • et al.
      Pharmacologic inhibition of 5-lipoxygenase improves memory, rescues synaptic dysfunction, and ameliorates tau pathology in a transgenic model of tauopathy.
      ).
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