Fibroblast growth factor 21 ameliorates neurodegeneration in rat and cellular models of Alzheimer’s disease
Song Chen,
Su-Ting Chen,
Yan Sun,
Zheng Xu,
Ying Wang,
Si-Yuan Yao,
Wen-Bing Yao,
Xiang-Dong Gao
Affiliations
Song Chen
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Su-Ting Chen
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Yan Sun
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Zheng Xu
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Ying Wang
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Si-Yuan Yao
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Wen-Bing Yao
Corresponding authors.; Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Xiang-Dong Gao
Corresponding authors.; Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Our understanding of the mechanisms underlying process in Alzheimer's disease (AD) is far from completion and new therapeutic targets are urgently needed. Recently, the link between dementia and diabetes mellitus (DM) prompted us to search for new therapeutic strategies from glucose metabolism regulators for neurodegeneration. Previous studies have indicated that fibroblast growth factor 21 (FGF21), an attractive and potential therapeutic treatment for DM, may exert diverse effects in the central nervous system. However, the specific biological function and mechanisms of FGF21 on AD is still largely unknown. We report here a study in vivo and in vitro of the neuroprotective effects of FGF21 on cell apoptosis, tau hyperphosphorylation and oxidative stress induced by amyloid β-peptide 25–35. In the present study, the results also further provided evidence for molecular mechanisms by which FGF21 exerted its beneficial effects in neuron and suggested that the regulation of protein phosphatase 2A / mitogen-activated protein kinases / hypoxia-inducible factor-1α pathway may play a key role in mediating the neuroprotective effects of FGF21 against AD-like pathologies. Keywords: Fibroblast growth factor 21, Alzheimer's disease, Tau, Oxidative stress, Mitogen-activated protein kinases
