Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
J Mol Endocrinol. 2011 Jun 8;46(3):R83-92. doi: 10.1530/JME-10-0125. Print 2011 Jun.
Neurotrophic factors are small proteins necessary for neuron survival and maintenance of phenotype. They are considered as promising therapeutic tools for neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF) protects catecholaminergic cells from toxic insults; thus, its potential therapeutic applicability in Parkinson's disease has been intensely investigated. In recent years, there have been major advances in the analysis of GDNF signaling pathways in peripheral neurons and embryonic dopamine mesencephalic cells. However, the actual physiological role of GDNF in maintaining catecholaminergic central neurons during adulthood is only starting to be unraveled, and the mechanisms whereby GDNF protects central brain neurons are poorly known. In this study, we review the current knowledge of GDNF expression, signaling, and function in adult brain, with special emphasis on the genetic animal models with deficiency in the GDNF-dependent pathways.
神经营养因子是维持神经元存活和表型所必需的小蛋白。它们被认为是治疗神经退行性疾病的有前途的治疗工具。胶质细胞源性神经营养因子（GDNF）可保护儿茶酚胺能细胞免受毒性损伤；因此，其在帕金森病中的潜在治疗应用已受到广泛研究。近年来，外周神经元和胚胎多巴胺中脑细胞中 GDNF 信号通路的分析取得了重大进展。然而，GDNF 在成年期维持儿茶酚胺能中枢神经元中的实际生理作用才刚刚开始被揭示，GDNF 保护中枢脑神经元的机制知之甚少。在这项研究中，我们综述了 GDNF 在成年脑中的表达、信号转导和功能的最新知识，特别强调了 GDNF 依赖性途径缺乏的遗传动物模型。
