内质网
碱性成纤维细胞生长因子
未折叠蛋白反应
神经保护
酪氨酸羟化酶
PI3K/AKT/mTOR通路
医学
下调和上调
蛋白激酶B
药理学
帕金森病
内分泌学
内科学
细胞生物学
信号转导
生长因子
化学
生物
受体
疾病
多巴胺
生物化学
基因
作者
Pingtao Cai,Jingjing Ye,Jingjing Zhu,Dan Liu,Daqing Chen,Xiaojie Wei,Noah R. Johnson,Zhouguang Wang,Hongyu Zhang,Guodong Cao,Jian Xiao,Junming Ye,Li Lin
标识
DOI:10.14336/ad.2016.0117
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress.
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