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Leukotrienes,

  • white blood cells
  • activity on 3 (tri) double bonded carbon chain (ene)

arachidonic acid

  • derived from Linoleic acid,
  • omega-6
  • pro-inflammitory response
  • low glutathione
  • astham attack
  • diabetic crisis

Released from lipid bilayer

Arachidonic Acid Pathway...Best Explanation!

Zileuton

  • a hydroxyurea containing molecule
  • asthma
  • leukemia
  • dementia

 

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Mol Neurobiol

. 2019 Feb;56(2):1211-1220.
doi: 10.1007/s12035-018-1124-7. Epub 2018 Jun 7.

Learning Impairments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes

Biosynthesis: Role of the cdk5 Kinase Pathway
Phillip F Giannopoulos  1 , Jian Chiu  1 , Domenico Praticò  2
Affiliations

    PMID: 29881943 DOI: 10.1007/s12035-018-1124-7


Abstract

Previous studies showed that the leukotrienes pathway is increased in human tauopathy and that its manipulation may modulate the onset and development of the pathological phenotype of tau transgenic mice. However, whether interfering with leukotrienes biosynthesis is beneficial after the behavioral deficits and the neuropathology have fully developed in these mice is not known. To test this hypothesis, aged tau transgenic mice were randomized to receive zileuton, a specific leukotriene biosynthesis inhibitor, or vehicle starting at 12 months of age for 16 weeks and then assessed in their functional and pathological phenotype. Compared with baseline, we observed that untreated tau mice had a worsening of their memory and spatial learning. By contrast, tau mice treated with zileuton had a reversal of these deficits and behaved in an undistinguishable manner from wild-type mice. Leukotriene-inhibited tau mice had an amelioration of synaptic integrity, lower levels of neuroinflammation, and a significant reduction in tau phosphorylation and pathology, which was secondary to an involvement of the cdk5 kinase pathway. Taken together, our findings represent the first demonstration that the leukotriene biosynthesis is functionally involved at the later stages of the tau pathological phenotype and represents an ideal target with viable therapeutic potential for treating human tauopathies.

Keywords: Behavior; Five-lipoxygenase; Leukotrienes; Neuroinflammation; Tauopathy; cdk5 kinase pathway.