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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。
GDNF is derived from microglial neurons and was first discovered as a resuscitator of midbrain dopaminergic neurons that promotes cell survival and increases dopamine neuronal cell size and axonal length. GDNF regulates cellular activity through its interaction with the anchoring protein cell surface receptor, glycosylphosphatidylinositol. The GDNF family a-1 receptor promotes cell survival, neurite growth, and synaptic development through transmembrane tyrosine receptors or neuronal cell adhesion molecules. Subsequent studies suggest that GDNF may be able to revive a variety of nerve cells in both the juvenile and the adult brain and is associated with the resurrection, migration and differentiation of some peripheral nerves. Various experimental models of cerebral ischemia confirmed the neuroprotective effects of exogenous GDNF on the lesion and the whole brain, including the application of trophic factor topically, the delivery of GDNF gene by viral vectors and the transplantation of GDNF-expressing cells. Recent studies have also confirmed that GDNF not only has nourishment and protective effects on dopaminergic neurons, central and peripheral nervous system motility, sensory neurons and autonomic neurons, but also on the non-nervous system. This article will focus on different strategies and mechanisms for these GDNF roles.