title: Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice.
  
  
  METHODS
  Mice were 3 months at the beginning of the study.
  
  
  METHODS
  Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip).
  
  
  METHODS
  Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis.
  
  
  RESULTS
  Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1-42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals.
  
  
  CONCLUSIONS
  Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy. abitto@unime.it.
authors.forename: Alessandra
authors.identifier: http://orcid.org/0000-0001-9300-7532
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giuliani
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pallio
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy.
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vandini
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Canalini
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Zaffe
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ottani
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Rinaldi
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of Biomedical Sciences, Morphological and Functional Images, University of Messina, Via C. Valeria, Torre Biologica 1st floor, 98125, Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D053583:Interleukin-1beta / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008822:Mice, Transgenic; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D053583:Interleukin-1beta; D016859:Lipoxygenase Inhibitors; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; C492716:Nlrp3 protein, mouse; C544478:flavocoxid; D016875:tau Proteins; D007975:Leukotriene B4; D002392:Catechin; D015232:Dinoprostone
keywords: Alzheimer; Baicalin; Catechin; Memory; NLRP3; Neurodegeneration