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Title: Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
Author: Ettcheto Arriola, Miren
Sánchez-López, E. (Elena)
Pons, Laura
Busquets Figueras, Oriol
Olloquequi González, Jordi
Beas Zárate, Carlos
Pallàs i Llibería, Mercè, 1964-
García López, María Luisa
Auladell i Costa, M. Carme
Folch, Jaume
Camins Espuny, Antoni
Keywords: Malaltia d'Alzheimer
Hipocamp (Cervell)
Receptors d'insulina
Alzheimer's disease
Hippocampus (Brain)
Insulin receptors
Issue Date: 15-Jun-2017
Publisher: Elsevier B.V.
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.
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It is part of: Redox Biology, 2017, vol. 13, p. 345 -352
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ISSN: 2213-2317
Appears in Collections:Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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