Induced dopaminergic neurons: A new promise for Parkinson's disease.
Induced dopaminergic neurons: A new promise for Parkinson's disease.
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诱导的多巴胺能神经元：帕金森氏病的新希望。
DOI：
10.1016/j.redox.2017.01.009
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发表时间：
2017-04
期刊：
影响因子：
11.4
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Xu Z;Chu X;Jiang H;Schilling H;Chen S;Feng J
帕金森病（PD）的运动症状是由黑质多巴胺能（DA）神经元的选择性丧失引起的。PD的细胞替代疗法主要集中在源自人胎儿中脑组织、人胚胎干细胞（hESC）或人诱导多能干细胞（iPSC）的中脑DA神经元。人成纤维细胞直接转化为诱导的多巴胺能神经元的最新进展为PD的移植研究和疾病建模提供了新的机会。iDA神经元在短时间内直接从人成纤维细胞产生，绕过了人多能干细胞的漫长分化过程和对潜在致瘤性有丝分裂细胞的担忧。它们在帕金森病动物模型中表现出功能性多巴胺能神经传递并缓解运动症状。在这篇综述中，我们将讨论这一最新进展及其对帕金森病研究和治疗的影响。成纤维细胞可以通过转录因子直接转化为诱导的多巴胺能神经元。许多不同类型的细胞可以在体外和体内转化为诱导神经元。适当的细胞培养条件增强了向诱导神经元的直接转化。G1期阻滞和p53衰减可增强向诱导神经元的转化。iDA神经元是用于PD研究和治疗的有前途的工具。
Motor symptoms that define Parkinson’s disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells. They exhibit functional dopaminergic neurotransmission and relieve locomotor symptoms in animal models of Parkinson’s disease. In this review, we will discuss this recent development and its implications to Parkinson’s disease research and therapy. Fibroblasts can be directly converted to induced dopaminergic neurons by transcription factors. Many different types of cells can be converted to induced neurons in vitro and in vivo. Appropriate cell culture conditions enhance the direct conversion to induced neurons. The conversion to induced neurons is enhanced by G1 arrest and p53 attenuation. iDA neurons is a promising tool for PD research and therapy.