鼠骨髓源神经干细胞向多巴胺能神经元定向诱导分化
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摘要
一、概述。
帕金森病(Parkinson Disease，PD)是一种中老年人常见的以黑质纹状体区多巴胺能神经元进行性缺失为特征的中枢神经系统变性疾病，其特征是震颤、肌强直、运动减少。病理改变以黑质致密层多巴胺神经元部分缺失、神经元中有路易小体(Lewy body，LB)形成等为特点。其发病率在整体人群为0.1％，在65岁以上人群高达1％。随着社会老龄化，帕金森病的发病率和致残率有增多趋势。近来的研究发现孤儿核受体超家族的成员之一的Nurr1(Nuclear related receptor 1，Nurr1)基因对于中脑多巴胺神经元的发育和存活非常重要，由此展开了Nurr1与多巴胺神经元发育以及帕金森病发病关系的研究。
Nurr1是神经祖细胞外源性TH的转录活化因子和多巴胺转运体的转录活化因子，Nurr1是诱导各个发育阶段和区域的中枢神经系统祖细胞分化为多巴胺能神经元的关键因子。Nurr1的缺失决定性地改变了中脑多巴胺能神经元的正常发育，导致多巴胺特异性标志丧失及多巴胺递质缺乏，多巴胺前体细胞发育停滞，不能分化成正常的多巴胺细胞或在发育过程中逐渐凋亡。Nurr1基因多态性可能是典型帕金森病的一个重要的危险基因因素。
近年来神经干细胞(Neural Stem Cells，NSCs)在PD的实验治疗研究中越来越受到重视。NSCs应用于PD的研究基于它的生物学特性。①、发育、分化和成熟的过程中不表达主要组织相容性复合体(MHC)Ⅰ类或Ⅱ类抗原，因此具有极低或无免疫原性，使其在异体移植后免受宿主的排斥，有助于其长期存活，
1. Overview
Parkinson Disease (PD) is a degenerative disease of the central nervous system common in middle-aged old people characterized by progressive deficiency of dopaminergic neurons in nigrostriatal area, with characteristics of tremor, myotonia and hypokinesia. The pathological changes are characterized by deficiency of dopaminergic neurons in substantia nigra compacta and formation of Lewy body (LB) in neurons. The overall incidence is about 0.1%, while the incidence in population over 65 years is 1%. With the aging of society, the incidence and disabling rate of Parkinson Disease tends to increase. Recent studies have found that orphan nuclear related receptor 1 ( Nurr1) gene plays an important role in the development and survival of mesencephalic dopaminergic neurons, therefore, many studies on relations between Nurrl and development of dopaminergic neurons as well as occurrence of Parkinson Disease have been carried out.
Nurrl is a transcriptional activation factor of exogenous TH of neural progenitor cells and dopamine transporter. Nurrl is the key factor in inducing progenitor cells of the central nervous system in each developmental stage and area to differentiate into dopaminergic neurons. Deficiency of Nurrl decisively changes the normal development of mesencephalic dopaminergic neurons, resulting in the loss of dopamine specific marker and deficiency of dopamine transmitter, and precursor cells' arrest of development, failure of differentiation into normal dopamine cells or gradual apoptosis in development process. The polymorphism of Nurrl gene may be
帕金森病(Parkinson Disease，PD)是一种中老年人常见的以黑质纹状体区多巴胺能神经元进行性缺失为特征的中枢神经系统变性疾病，其特征是震颤、肌强直、运动减少。病理改变以黑质致密层多巴胺神经元部分缺失、神经元中有路易小体(Lewy body，LB)形成等为特点。其发病率在整体人群为0.1％，在65岁以上人群高达1％。随着社会老龄化，帕金森病的发病率和致残率有增多趋势。近来的研究发现孤儿核受体超家族的成员之一的Nurr1(Nuclear related receptor 1，Nurr1)基因对于中脑多巴胺神经元的发育和存活非常重要，由此展开了Nurr1与多巴胺神经元发育以及帕金森病发病关系的研究。
Nurr1是神经祖细胞外源性TH的转录活化因子和多巴胺转运体的转录活化因子，Nurr1是诱导各个发育阶段和区域的中枢神经系统祖细胞分化为多巴胺能神经元的关键因子。Nurr1的缺失决定性地改变了中脑多巴胺能神经元的正常发育，导致多巴胺特异性标志丧失及多巴胺递质缺乏，多巴胺前体细胞发育停滞，不能分化成正常的多巴胺细胞或在发育过程中逐渐凋亡。Nurr1基因多态性可能是典型帕金森病的一个重要的危险基因因素。
近年来神经干细胞(Neural Stem Cells，NSCs)在PD的实验治疗研究中越来越受到重视。NSCs应用于PD的研究基于它的生物学特性。①、发育、分化和成熟的过程中不表达主要组织相容性复合体(MHC)Ⅰ类或Ⅱ类抗原，因此具有极低或无免疫原性，使其在异体移植后免受宿主的排斥，有助于其长期存活，
1. Overview
Parkinson Disease (PD) is a degenerative disease of the central nervous system common in middle-aged old people characterized by progressive deficiency of dopaminergic neurons in nigrostriatal area, with characteristics of tremor, myotonia and hypokinesia. The pathological changes are characterized by deficiency of dopaminergic neurons in substantia nigra compacta and formation of Lewy body (LB) in neurons. The overall incidence is about 0.1%, while the incidence in population over 65 years is 1%. With the aging of society, the incidence and disabling rate of Parkinson Disease tends to increase. Recent studies have found that orphan nuclear related receptor 1 ( Nurr1) gene plays an important role in the development and survival of mesencephalic dopaminergic neurons, therefore, many studies on relations between Nurrl and development of dopaminergic neurons as well as occurrence of Parkinson Disease have been carried out.
Nurrl is a transcriptional activation factor of exogenous TH of neural progenitor cells and dopamine transporter. Nurrl is the key factor in inducing progenitor cells of the central nervous system in each developmental stage and area to differentiate into dopaminergic neurons. Deficiency of Nurrl decisively changes the normal development of mesencephalic dopaminergic neurons, resulting in the loss of dopamine specific marker and deficiency of dopamine transmitter, and precursor cells' arrest of development, failure of differentiation into normal dopamine cells or gradual apoptosis in development process. The polymorphism of Nurrl gene may be
引文
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