Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways
Authors: Merce Pallas
Maria Luisa García
Miren Ettcheto
Laura Pons
Carme Auladell
Elena Sánchez-López
Carlos Beas-Zarate
Antoni Camins
Jordi Olloquequi
Oriol Busquets
Jaume Folch
Journal: Redox Biology (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: APPSwe/PS1dE9; Alzheimer's disease; Dexibuprofen; Hippocampus; Insulin receptor
Affiliations: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia i Ciencias de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain; Institut de Neurociencias, University of Barcelona, Spain., Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Unitat de Farmacia, Tecnologia Farmacèutica i Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Spain., Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia i Ciencias de l'Alimentació, Universitat de Barcelona, Barcelona, Spain., Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile., Laboratorio de Regeneración y Desarrollo Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Jalisco, Mexico., Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia i Ciencias de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Institut de Neurociencias, University of Barcelona, Spain., Unitat de Farmacia, Tecnologia Farmacèutica i Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Spain., Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain., Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain., Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia i Ciencias de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Institut de Neurociencias, University of Barcelona, Spain. Electronic address: .

Abstract:  The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks. 

Retracted: No

PubPeer comments:
 There appears to be a possible splice in Figure 5A. Could the authors please provide the uncropped original scan? *** ![file] ![file] ,