title: Reduction of amyloid-β deposition and attenuation of memory deficits by tolfenamic acid.
abstract: We have previously reported that tolfenamic acid treatment decreases the amyloidogenic proteins in C57BL/6 and in old hemizygous R1.40 transgenic mice via the degradation of the transcription factor specificity 1 protein (Sp1). The lowering of amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in hemizygous R1.40 transgenic mice was accompanied by reversal of the identified spatial reference and working memory deficits observed in the mouse model. In this study, we examined the ability of tolfenamic acid to reduce the amyloid plaque burden, as well as to ameliorate spatial learning and memory deficits in homozygous R1.40 mice. Results from immunohistochemical analysis indicated that tolfenamic acid treatment resulted in a profound decrease in cerebral Aβ plaque burden that was accompanied by improvements in spatial working memory assessed by spontaneous alternation ratio in the Y-maze. These results provide further evidence that tolfenamic acid could be utilized as a repurposed drug to modify Alzheimer's disease pathogenesis.
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors.forename: Gehad M
authors.initials: GM
authors.lastname: Subaiea
authors.affiliation: Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.
authors.forename: Aseef H
authors.initials: AH
authors.lastname: Ahmed
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors.forename: Lina I
authors.initials: LI
authors.lastname: Adwan
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
mesh_terms: D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D013997:Time Factors; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid
keywords: AD transgenic mouse model; Alzheimer's disease; Morris water maze; Y-maze; amyloid-β plaque burden; immunohistochemistry; learning and memory; tolfenamic acid