Kotzbauer P T, Lampe P A, Heuckeroth R O, Golden J P, Creedon D J, Johnson E M, Milbrandt J
Division of Laboratory Medicine, Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nature. 1996 Dec 5;384(6608):467-70. doi: 10.1038/384467a0.
The normal development of the vertebrate nervous system entails the death of 30-70% of the neurons originally generated in most neuronal populations. This naturally occurring cell death is regulated by specific neurotrophic factors that promote neuronal survival and which are produced in limiting quantities by target cells, glial cells and neurons. These factors are also of potential utility as therapeutic agents for neurodegenerative diseases. Here we describe the purification and cloning of a new neurotrophic factor, identified on the basis of its ability to support the survival of sympathetic neurons in culture. This factor, neurturin, is structurally related to glial-cell-line-derived neurotrophic factor (GDNF). These factors can each activate the MAP kinase signalling pathway in cultured sympathetic neurons and support the survival of sympathetic neurons, as well as of sensory neurons of the nodose and dorsal root ganglia. Thus, neurturin and GDNF together now define a new family of neurotrophic factors.
脊椎动物神经系统的正常发育需要大多数神经元群体中最初生成的神经元有30% - 70%死亡。这种自然发生的细胞死亡受特定神经营养因子调控，这些因子促进神经元存活，且由靶细胞、神经胶质细胞和神经元以有限量产生。这些因子作为神经退行性疾病的治疗药物也具有潜在用途。在此，我们描述了一种新神经营养因子的纯化和克隆，该因子是根据其在培养中支持交感神经元存活的能力而鉴定出来的。这种因子，即神经营养素，在结构上与胶质细胞系源性神经营养因子（GDNF）相关。这些因子各自都能在培养的交感神经元中激活丝裂原活化蛋白激酶信号通路，并支持交感神经元以及结状神经节和背根神经节感觉神经元的存活。因此，神经营养素和GDNF共同定义了一个新的神经营养因子家族。
