Wei Xiaojie, He Songbin, Wang Zhouguang, Wu Jiamin, Zhang Jinjing, Cheng Yi, Yang Jie, Xu Xinlong, Chen Zaifeng, Ye Junmin, Chen Li, Lin Li, Xiao Jian
Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo, Zhejiang, 315300, PR China.
Department of Neurology, Zhoushan Hospital, Wenzhou Medical University Zhoushan, Zhejiang, 316000, PR China.
Am J Transl Res. 2014 Nov 22;6(6):664-77. eCollection 2014.
Parkinson's disease (PD) is a degenerative disorder of the central nervous system and is characterized by motor system disorders resulting in loss of dopamine producing brain cells. Acidic fibroblast growth factor, also called FGF1, promotes the survival of neurons. The aims of the present study were to confirm FGF1 could protect neurons cultures from 6-hydroxydopamine (6-OHDA) toxicity in vitro and in vivo. Our results demonstrated FGF1 administration improved the motor function recovery, increased the TH-positive neurons survival and up-regulated the levels of neurotransmitters in PD rats. Meanwhile, FGF1 prevents the death of DA neuron at least in part by reducing the levels of α-synuclein and ER stress. The administration of FGF1 activated downstream signals PI3K/Akt and ERK1/2. In conclusion, FGF1 diminished α-synuclein neurotoxicity by down regulating ER stress mediators and the level of apoptosis, and these effects may underlying the activation of the PI3K/Akt and ERK1/2 signal pathway.
帕金森病（PD）是一种中枢神经系统退行性疾病，其特征是运动系统紊乱，导致产生多巴胺的脑细胞丧失。酸性成纤维细胞生长因子，也称为FGF1，可促进神经元的存活。本研究的目的是证实FGF1在体外和体内均可保护神经元培养物免受6-羟基多巴胺（6-OHDA）毒性的影响。我们的结果表明，给予FGF1可改善帕金森病大鼠的运动功能恢复，增加TH阳性神经元的存活，并上调神经递质水平。同时，FGF1至少部分地通过降低α-突触核蛋白水平和内质网应激来防止多巴胺能神经元死亡。给予FGF1可激活下游信号PI3K/Akt和ERK1/2。总之,FGF1通过下调内质网应激介质和细胞凋亡水平减轻α-突触核蛋白神经毒性，这些作用可能是PI3K/Akt和ERK1/2信号通路激活的基础。
