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.
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.
Redox Biol. 2019 Apr;22:101133. doi: 10.1016/j.redox.2019.101133. Epub 2019 Feb 1.
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.
我们对阿尔茨海默病（AD）发病机制的理解还远未完成，迫切需要新的治疗靶点。最近，痴呆症与糖尿病（DM）之间的联系促使我们从葡萄糖代谢调节剂中寻找针对神经退行性变的新治疗策略。先前的研究表明，成纤维细胞生长因子 21（FGF21）是一种有吸引力的、有潜力的 DM 治疗药物，它可能在中枢神经系统中发挥多种作用。然而，FGF21 对 AD 的具体生物学功能和机制仍知之甚少。我们在这里报告了 FGF21 在体内和体外对淀粉样β肽 25-35 诱导的细胞凋亡、tau 过度磷酸化和氧化应激的神经保护作用的研究。在本研究中，结果还进一步为 FGF21 发挥其在神经元中的有益作用的分子机制提供了证据，并表明蛋白磷酸酶 2A/丝裂原激活蛋白激酶/缺氧诱导因子-1α通路的调节可能在介导 FGF21 对 AD 样病变的神经保护作用中起关键作用。
