Department of Neurology, Columbia University , New York, NY, USA.
Department of Neurology, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Mol Ther Methods Clin Dev. 2016 Sep 21;3:16062. doi: 10.1038/mtm.2016.62. eCollection 2016.
The use of viral vectors to transfect postmitotic neurons has provided an important research tool, and it offers promise for treatment of neurologic disease. The utility of vectors is enhanced by the use of selective promoters that permit control of the cellular site of expression. One potential clinical application is in the neurorestorative treatment of Parkinson's disease by the induction of new axon growth. However, many of the genes with an ability to restore axons have oncogenic potential. Therefore, clinical safety would be enhanced by restriction of expression to neurons affected by the disease, particularly dopamine neurons. To achieve this goal we have evaluated in vivo three partial sequences of the promoter for human tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis. All sequences induced expression in dopamine neurons. None of them induced expression in glia or in nondopaminergic neurons in striatum or cortex. We conclude that these sequences have potential use for targeting dopamine neurons in research and clinical applications.
病毒载体转染有丝分裂后神经元的应用提供了一个重要的研究工具，为治疗神经疾病带来了希望。通过使用选择性启动子来控制细胞表达部位，可以增强载体的实用性。一个潜在的临床应用是通过诱导新的轴突生长来治疗帕金森病的神经修复。然而，许多具有恢复轴突能力的基因具有致癌潜力。因此，通过将表达限制在受疾病影响的神经元上，特别是多巴胺神经元，将提高临床安全性。为了实现这一目标，我们评估了人类酪氨酸羟化酶启动子的三个部分序列，该基因是儿茶酚胺合成的限速酶。所有序列均诱导多巴胺神经元表达。它们都没有诱导胶质细胞或纹状体或皮层中的非多巴胺神经元表达。我们得出结论，这些序列在研究和临床应用中具有靶向多巴胺神经元的潜力。
