PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease

Experimental Neurology
Wei-Chun J HsuFernanda Laezza

Abstract

Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation. We used a combination of mass spectrometry, confocal imaging, electrophysiology and split-luciferase assay and in vitro phosphorylation and Ingenuity Pathway Analysis. Using an unbiased, quantitative nano-LC-MS/MS screening, we searched for potential molecular targets of the RSG-dependent rescue of DG granule neurons. We found that S226 phosphorylation of fibroblast growth factor 14 (FGF14), an accessory protein of the voltage-gated Na+ (Nav) channels required for neuronal firing, was reduced in Tg2576 mice upon treatment with RSG. Using confocal microscopy, we confirmed that the Tg2576 condition decreased PanNav channels at the AIS of the DG, and that RSG treatment of Tg2576 mice reversed the reduction in PanNav channels. Analysis from previously published dat...Continue Reading

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Citations

Nov 23, 2019·Pharmacogenomics·Willian Abraham da SilveiraGary Hardiman
May 2, 2018·Journal of Alzheimer's Disease : JAD·Jung Hyun LeeKelly T Dineley
Oct 12, 2018·Current Medicinal Chemistry·Mentor SopjaniMiribane Dërmaku-Sopjani
May 1, 2021·International Journal of Molecular Sciences·Virginie BotteroJudith A Potashkin
Jul 20, 2021·Frontiers in Molecular Neuroscience·Jessica Di ReFernanda Laezza
Jan 24, 2018·ACS Chemical Neuroscience·Syed R AliFernanda Laezza
Jul 1, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Paul A WadsworthFernanda Laezza
Nov 4, 2021·Molecular Biology Reports·Ramy AlamSanaa Nabha

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