胶质源性神经营养因子对不同组织细胞的影响

GDNF来自于小胶质神经元,首先作为中脑多巴胺能神经元的复活因子被发现,可促进细胞存活,并有增加多巴胺神经元细胞大小及轴突长度的作用。GDNF通过与锚定蛋白细胞表面受体糖基磷脂酰肌醇的相互作用来调节细胞活性。GDNF家族a-1受体,通过跨膜酪氨酸受体或者神经元细胞黏附分子,来促进细胞存活,神经突生长,以及突触发育。后续的研究提示,无论未成年还是成体大脑,GDNF对多种神经细胞都有复活的作用,并与一些周围神经复活、迁移、分化相关。不同的脑缺血实验模型均证实了外源性GDNF对于病灶部位及全脑的神经保护作用,包括局部应用营养因子,利用病毒载体运载GDNF基因以及移植表达GDNF的细胞。近来研究还证实,GDNF不仅对多巴胺能神经元,中枢和周围神经系统的运动、感觉神经元,以及自主神经元有营养和保护作用,对于非神经系统也有不同调节作用。本文将重点讨论这些GDNF作用的不同策略以及机制。

The Influence of GDNF in Different Tissues and Cells

Glial cell line-derived neurotrophic factor (GDNF) was identified froma glial cell line based on its ability to promote the survival aswell as the increase in cell size and neurite length in mesencephalic dopaminergic neurons . Since not sufficient effect was observed, GDNF was originally believed to be a selective survival factor dopaminergic neurons. GDNF regulates cellular activity through interaction with glycosyl-phosphatidylinositol-anchored cell surface receptors, GDNF family receptor-a1, which might signal through the transmembrane Ret tyrosine receptors or the neural cell adhesion molecule, to promote cell survival, neurite outgrowth, and synaptogenesis. However, additional studies showed that GDNF also supports the survival of various neurons, and regulates the survival, migration, and differentiation of several peripheral neurons. The effects of GDNF on neuronal survival were shown both during development and in the adult brain. The neuroprotective effect of exogenous GDNF has been shown in different experimental models of focal and global brain ischemia, by local administration of the trophic factor, using viral vectors carrying the GDNF gene and by transplantation of GDNF-expressing cells. Recent researches demonstrate that GDNF support the effect of nutrition and protection of neurons, including dopaminergic sensory, motor, sympathetic and parasympathetic neurons. GDNF has further critical roles outside the nervous system. These different strategies and the mechanisms of GDNF are discussed in this review.