Ibáñez Carlos F, Andressoo Jaan-Olle
Department of Physiology, National University of Singapore, Singapore 117597, Singapore; Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Department of Neuroscience, Karolinska Institute, Stockholm S-17177, Sweden; Stellenbosch Institute for Advanced Study, Wallenberg Research Centre at Stellenbosch University, Stellenbosch 7600, South Africa.
Institute of Biotechnology, University of Helsinki, Helsinki 00014, , Finland.
Neurobiol Dis. 2017 Jan;97(Pt B):80-89. doi: 10.1016/j.nbd.2016.01.021. Epub 2016 Jan 29.
A targeted effort to identify novel neurotrophic factors for midbrain dopaminergic neurons resulted in the isolation of GDNF (glial cell line-derived neurotrophic factor) from the supernatant of a rat glial cell line in 1993. Over two decades and 1200 papers later, the GDNF ligand family and their different receptor systems are now recognized as one of the major neurotrophic networks in the nervous system, important for the development, maintenance and function of a variety of neurons and glial cells. The many ways in which the four members of the GDNF ligand family can signal and function allow these factors to take part in the control of multiple types of processes, from neuronal survival to axon guidance and synapse formation in the developing nervous system, to synaptic function and regenerative responses in the adult. In this review, we will briefly summarize basic aspects of GDNF signaling mechanisms and receptor systems and then review our current knowledge of the physiology of GDNF activities in the central nervous system, with an eye to its relevance for neurodegenerative and neuropsychiatric diseases.
1993年，一项旨在寻找中脑多巴胺能神经元新型神经营养因子的针对性研究，从大鼠胶质细胞系的上清液中分离出了胶质细胞源性神经营养因子（GDNF）。二十多年过去了，相关论文发表了1200多篇，如今GDNF配体家族及其不同的受体系统被公认为神经系统中主要的神经营养网络之一，对多种神经元和胶质细胞的发育、维持及功能至关重要。GDNF配体家族的四个成员能够通过多种方式进行信号传导并发挥作用，使这些因子参与多种类型过程的调控，从发育中的神经系统中的神经元存活、轴突导向和突触形成，到成体中的突触功能和再生反应。在这篇综述中，我们将简要总结GDNF信号传导机制和受体系统的基本方面，然后回顾我们目前对GDNF在中枢神经系统中生理活性的认识，着眼于其与神经退行性疾病和神经精神疾病的相关性。
