Cortés Daniel, Carballo-Molina Oscar A, Castellanos-Montiel María José, Velasco Iván
Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de MéxicoMéxico City, Mexico.
Laboratorio de Reprogramación Celular del IFC-UNAM, Instituto Nacional de Neurología y NeurologíaMéxico City, Mexico.
Front Mol Neurosci. 2017 Aug 22;10:258. doi: 10.3389/fnmol.2017.00258. eCollection 2017.
Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons. GDNF also induces the acquisition of a dopaminergic phenotype by increasing the expression of Tyrosine Hydroxylase (TH), Nurr1 and other proteins that confer this identity and promote further dendritic and electrical maturation. In motor neurons (MNs), GDNF not only promotes proliferation and maturation but also participates in regenerating damaged axons and modulates the neuromuscular junction (NMJ) at both presynaptic and postsynaptic levels. Moreover, GDNF modulates the rate of neuroblastoma (NB) and glioblastoma cancer cell proliferation. Additionally, the presence or absence of GDNF has been correlated with conditions such as depression, pain, muscular soreness, etc. Although, the precise role of GDNF is unknown, it extends beyond a survival effect. The understanding of the complete range of properties of this trophic molecule will allow us to investigate its broad mechanisms of action to accelerate and/or improve therapies for the aforementioned pathological conditions.
胶质细胞系源性神经营养因子（GDNF）最初被鉴定为一种对多巴胺能神经元（DANs）具有促存活作用的分子。此后，人们还发现其他细胞不仅对GDNF作为一种存活因子有反应，而且作为一种支持其他细胞功能的蛋白质也有反应，这些功能包括增殖、分化、成熟、神经突生长以及其他一些研究较少的现象，本文将对此进行更广泛的描述。在发育过程中，GDNF有利于神经前体细胞向多巴胺能、运动、肠和肾上腺神经元的定向分化；此外，它还能促进其中一些神经元的轴突生长。GDNF还通过增加酪氨酸羟化酶（TH）、Nurr1和其他赋予这种特性并促进进一步树突和电成熟的蛋白质的表达，诱导获得多巴胺能表型。在运动神经元（MNs）中，GDNF不仅促进增殖和成熟，还参与受损轴突的再生，并在突触前和突触后水平调节神经肌肉接头（NMJ）。此外，GDNF调节神经母细胞瘤（NB）和胶质母细胞瘤癌细胞的增殖速率。此外，GDNF的存在与否与抑郁症、疼痛、肌肉酸痛等情况相关。尽管GDNF的确切作用尚不清楚，但其作用超出了存活效应。对这种营养分子完整特性范围的了解将使我们能够研究其广泛的作用机制，以加速和/或改善针对上述病理状况的治疗方法。
