Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c
Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c
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DOI：
10.1002/jnr.10592
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发表时间：
2003-05-15
影响因子：
4.2
通讯作者：
Itoh, N
中科院分区：
文献类型：
--
作者：
Ohmachi, S;Mikami, T;Itoh, N
黑质多巴胺能神经元的退化导致帕金森病。因此，多巴胺能神经元的神经营养因子具有重要的临床意义。成纤维细胞生长因子（FGF）-20优先在大鼠脑黑质致密部（SNPC）表达，显着增强中脑多巴胺能神经元的存活。在这里，我们研究了 FGF-20 对多巴胺能神经元的作用机制。 FGF-20 略微增强了中脑总神经元的存活率，表明它优先增强了多巴胺能神经元的存活率。通过原位杂交发现 FGF 受体 (FGFR)-1c 在 SNPC 的多巴胺能神经元中大量表达，但在其他中脑区域的神经元中表达水平低得多。还发现 FGF-20 与 BIAcore 系统以高亲和力结合 FGFR-1c。此外，FGF-20 激活丝裂原激活蛋白激酶 (MAPK) 途径，这是 FGF 的主要细胞内信号传导途径。 FGFR-1抑制剂SU5402和MAPK通路抑制剂PD98059也显着抑制FGF-20对MAPK通路的激活以及FGF-20的神经营养活性。目前的研究结果表明，FGF-20 信号通过 FGFR-1c 激活 MAPK 通路，在 SNPC 中多巴胺能神经元的存活中发挥重要作用。 (C) 2003 年 Wiley-Liss 公司
Degeneration of dopaminergic neurons of the substantia nigra causes Parkinson's disease. Therefore, neurotrophic factors for dopaminergic neurons are of substantial clinical interest. Fibroblast growth factor (FGF)-20 preferentially expressed in the substantia nigra pars compacta (SNPC) of the rat brain significantly enhanced the survival of midbrain dopaminergic neurons. Here we examined the mechanism of action of FGF-20 on dopaminergic neurons. FGF-20 slightly enhanced the survival of total neurons of the midbrain, indicating that it preferentially enhanced the survival of dopaminergic neurons. FGF receptor (FGFR)-1c was found to be expressed abundantly in dopaminergic neurons in the SNPC but at much lower levels in neurons of other midbrain regions by in situ hybridization. FGF-20 was also found to bind FGFR-1c with high affinity with the BIAcore system. Furthermore, FGF-20 activated the mitogen-activated protein kinase (MAPK) pathway, which is the major intracellular signaling pathway of FGFs. Both the FGFR-1 inhibitor SU5402 and the MAPK pathway inhibitor PD98059 also significantly inhibited the activation of the MAPK pathway by FGF-20 and the neurotrophic activity of FGF-20. The present findings indicate that the activation of the MAPK pathway by FGF-20 signaling through FGFR-1 c plays important roles in the survival of dopaminergic neurons in the SNPC. (C) 2003 Wiley-Liss, inc.