Murase Sachiko, McKay Ronald D
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2006 Sep 20;26(38):9750-60. doi: 10.1523/JNEUROSCI.2745-06.2006.
The specific expression of fibroblast growth factor 20 (FGF-20) in the adult substantia nigra and the association between FGF-20 mutations and Parkinson's disease provoked exploration of the function of this growth factor. We show by gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine hydroxylase in calbindin-negative neurons. In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1). These data show that FGF signals to elevate DA levels and protect the specific midbrain neuron type at most risk in Parkinson's patients.
成人大脑中黑质区域成纤维细胞生长因子20（FGF - 20）的特异性表达以及FGF - 20突变与帕金森病之间的关联引发了对这种生长因子功能的探索。我们通过体外功能获得和功能缺失实验表明，FGF - 20能促进帕金森病中优先丢失的钙结合蛋白阴性细胞亚群的存活并刺激多巴胺（DA）释放。FGF - 20在钙结合蛋白阴性神经元中选择性激活酪氨酸羟化酶。在成人大脑中黑质区域，钙结合蛋白阴性神经元特异性高表达FGFR1（FGF受体1）。这些数据表明，FGF通过信号传导提高多巴胺水平，并保护帕金森病患者中最易受损的特定中脑神经元类型。
