Henderson C E, Phillips H S, Pollock R A, Davies A M, Lemeulle C, Armanini M, Simmons L, Moffet B, Vandlen R A, Simpson LC corrected to Simmons L, Koliatsos V E, Rosenthal A
INSERM U.382, IBDM, Marseille, France.
Science. 1994 Nov 11;266(5187):1062-4. doi: 10.1126/science.7973664.
For survival, embryonic motoneurons in vertebrates depend on as yet undefined neurotrophic factors present in the limb bud. Members of the neurotrophin family are currently the best candidates for such neurotrophic factors, but inactivation of their receptor genes leads to only partial loss of motoneurons, which suggests that other factors are involved. Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture. GDNF messenger RNA was found in the immediate vicinity of motoneurons during the period of cell death in development. In vivo, GDNF rescues and prevents the atrophy of facial motoneurons that have been deprived of target-derived survival factors by axotomy. GDNF may therefore be a physiological trophic factor for spinal motoneurons. Its potency and specificity in vitro and in vivo also make it a good candidate for treatment of motoneuron disease.
脊椎动物胚胎运动神经元的存活依赖于肢芽中尚未明确的神经营养因子。神经营养因子家族成员目前是这类神经营养因子的最佳候选者，但它们受体基因的失活仅导致运动神经元部分丧失，这表明还有其他因子参与其中。胶质细胞系源性神经营养因子（GDNF）最初被鉴定为对多巴胺能神经元具有特异性的营养因子，结果发现它在支持培养的纯化胚胎大鼠运动神经元存活方面比神经营养因子的效力高75倍。在发育过程中的细胞死亡期，在运动神经元紧邻区域发现了GDNF信使核糖核酸。在体内，GDNF可挽救并防止因轴突切断而被剥夺了靶源性存活因子的面神经运动神经元发生萎缩。因此，GDNF可能是脊髓运动神经元的一种生理性营养因子。其在体外和体内的效力及特异性也使其成为治疗运动神经元疾病的良好候选药物。
