Author, as appears in the article.: Ettcheto M, Sánchez-López E, Pons L, Busquets O, Olloquequi J, Beas-Zarate C, Pallas M, García ML, Auladell C, Folch J, Camins A.

Department: Bioquímica i Biotecnologia

URV's Author/s: Folch Lopez, Jaume

Keywords: Tau Mitochondria Memory impairment Insulin receptor Hippocampus Dexibuprofen Atiinflamatory drug Appswe/ps1de9 Alzheimer's disease mitochondria memory impairment insulin receptor hippocampus dexibuprofen appswe/ps1de9 alzheimer's disease

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.

Thematic Areas: Química Organic chemistry Odontología Medicina ii Medicina i Farmacia Clinical biochemistry Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade Biochemistry & molecular biology Biochemistry Astronomia / física

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 22132317

Author's mail: jaume.folch@urv.cat

Author identifier: 0000-0002-5051-8858

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S2213231717302823

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Redox Biology. 13 345-352

APA: Ettcheto M, Sánchez-López E, Pons L, Busquets O, Olloquequi J, Beas-Zarate C, Pallas M, García ML, Auladell C, Folch J, Camins A. (2017). Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.. Redox Biology, 13(), 345-352. DOI: 10.1016/j.redox.2017.06.003

Article's DOI: 10.1016/j.redox.2017.06.003

Entity: Universitat Rovira i Virgili

Journal publication year: 2017

Publication Type: Journal Publications