胶质细胞源性神经营养因子受体

胶质细胞源性神经营养因子能够促进多种神经细胞特别是多巴胺能神经元及运动神经元存活。胶质细胞源性神经营养因子的信号传递受体是ＲＥＴ受体酪氨酸激酶,受体α亚基是它与ＲＥＴ相互作用的媒介。胶质细胞源性神经营养因子生物学活性的发挥需要ＲＥＴ与受体α亚基同时存在。     

胶质细胞源神经营养因子研究进展

叙述了新近纯化的胶质细胞源神经营养因子（ＧＤＮＦ）的生物功能及其在鼠胚胎的分布,着重介绍了该因子对损伤的多巴胺能神经元及运动神经元促进存活,修复损伤及再生的活性。     

胶质细胞源神经营养因子

胶质细胞源神经营养因子陈哲宇何成王成海（第二军医大学神经生物教研室,上海２００４３３）关键词胶质细胞源神经营养因子多巴胺能神经元运动神经元神经营养因子是指能够促进神经细胞存活、生长和分化的一类蛋白质。胶质细胞源神经营养因子（ＧＤＮＦ）,因其最初从大鼠...     

胶质细胞源性神经营养因子对疼痛的调节作用

胶质细胞源性神经营养因子(glial cell derived neurotrophic factor,GDNF)属转化生长因子β超家族成员,其成熟蛋白由134个氨基酸残基组成,而GDNF受体广泛分布于外周和中枢神经系统。GDNF不仅可以促进多巴胺能神经元、运动神经元的存活,对交感、副交感以及感觉神经元具有营养作用,还能够影响神经元的发育、分化并对非神经系统的发育也具有重要作用。近年来随着人们对疼痛认识的深入,疼痛的机制也不再限于神经元功能的改变,还受胶质细胞活化、多种营养因子、细胞因子及相应受体、离子通道等多方面因素的影响。为此,本文就近年来GDNF参与疼痛调节的相关研究进展做一简要综述。     

中脑星形胶质细胞源性神经营养因子

中脑星形胶质细胞源性神经营养因子（mesencephalic astrocyte-derived neurotrophic factor, MANF）是一种新型保守的神经营养因子,其结构和作用形式与传统的神经营养因子存在差异。MANF具有独特的三维结构,包含N端saposin样结构域和C端SAP（SAF-A/B, Acinus and PIAS, SAP）结构域,决定其特殊的作用形式。表达MANF的组织在哺乳动物体内分布广泛。在细胞内,MANF主要位于内质网腔,对于维持内质网稳态具有重要意义。在细胞外,MANF作为一种分泌蛋白质,不仅具有保护和促进多巴胺能神经元修复的功能,对包括胰岛β细胞、心肌细胞、视网膜神经节细胞等其他细胞类型也具有保护作用。此外,MANF还可通过调节炎症相关通路抑制炎症反应。研究显示,MANF在多种疾病中呈现出潜在的临床价值。本文将对MANF的结构、生理功能及其研究进展进行综述。     

胶质细胞源神经营养因子治疗帕金森病的研究

胶质细胞源神经营养因子治疗帕金森病的研究唐剑闻（华东师范大学生物系,上海２０００６２）刘健郑仲承（中国科学院上海生物化学研究所,上海２０００３１关键词胶质细胞源神经营养因子帕金森病基因治疗帕金森病（Ｐａｒｋｉｎｓｏｎ＇ｓｄｉｓｅａｓｅ,ＰＤ）是一种常...     

胶质细胞源性神经营养因子在不同年龄大鼠小脑及海马中的表达差异

目的观察胶质细胞源性神经营养因子（GDNF）在青年和老年大鼠小脑和海马中的表达特征。方法采用免疫组织化学方法显示GDNF在青年及老年大鼠小脑和海马的分布变化。应用计算机图像分析系统对免疫组织化学反应切片进行检测。结果青年组小脑蒲肯野细胞GDNF阳性反应明显强于老年组;但在青年和老年大鼠海马区,GDNF免疫细胞反应的差别并不明显。结论GDNF在蒲氏细胞内含量的增龄性变化提示它影响蒲肯野细胞及小脑其它神经元的功能与存活,对于小脑神经细胞的老化有重要意义。     

重组人胶质细胞源性神经营养因子的生物学活性研究

从人星形胶质细胞瘤BT-325细胞中克隆胶质细胞源性神经营养因子(GDNF) cDNA序列.以大肠杆菌作为表达系统,GDNF蛋白在大肠杆菌JM103中获得了高效表达;表达产物经纯化、复性后,以8日龄鸡胚背根节（DRG）、14日龄胎鼠脊髓前角运动神经元以及新生大鼠大脑皮层胶质细胞作为实验材料,研究了GDNF的生物学活性,结果表明： rhGDNF可有效地促进DRG突起的生长,rhGDNF对体外培养的运动神经元表现出明显的促突起生长作用,并可显著提高体外培养运动神经元的存活率,rhGDNF 对体外培养的胶质细胞具有促增殖作用.     

胚胎神经干细胞移植及胶质细胞源性神经营养因子对大鼠脊髓损伤的修复作用

将胚胎神经干细胞(neural stem cells,NSCs)移植至成年大鼠损伤的脊髓,观察移植后NSCs的存活、迁移以及损伤后的功能恢复。实验结果显示：动物NSCs移植4周后,斜板实验平均角度和运动评分结果比对照组均有明显增高(P＜0．05),而脊髓损伤(spinal cord injury,SCI)处的空洞面积显著减小(P＜0．05);在NSCs中加入胶质细胞源性的神经营养因子(glial cell line-derived neurotrophic factor,GDNF)后,上述改变更加显著。移植后的NSCs不仅能存活,而且向损伤的头端和尾端迁移达3mm之远。这些结果表明,移植的NSCs不仅可以存活、迁移,还可减小SCI空洞面积,促进动物神经功能的恢复;此外,我们的结果还表明GDNF对SCI功能恢复有促进作用。     

胶质细胞原神经营养因子研究进展

叙述了新近纯化的胶质细胞源神经营养因子（GDNF）的生物功能及其在鼠胚中的分布,着重介绍了该因子对损伤的多巴胺能神经元及运动神经元促进存活、修复损伤及再生的活性.     

胶质细胞衍生的神经营养因子成熟肽基因的克隆、表达及纯化的研究

通过ＰＣＲ的方法克隆了胶质细胞衍生的神经营养因子（ｇｌｉａｃｅｌ－ｌｉｎｅｄｅｒｉｖｅｄｎｅｕ－ｒｏｔｒｏｐｈｉｃｆａｃｔｏｒ,ＧＤＮＦ）成熟肽的基因,并将其连接到Ｅ．ｃｏｌｉ高效表达载体ｐＥＴ１６ｂ,在Ｅ．ｃｏｌｉ中获得高效表达．表达蛋白占菌体总蛋白２１％以上,以包涵体形式存在,经体外复性后用金属螯合亲和层析的方法得到具有较高纯度和活性ｒｈＧＤＮＦ．     

The Proform of Glia Cell Line-Derived Neurotrophic Factor: a Potentially Biologically Active Protein

Growing evidences have revealed that the proforms of several neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), by binding to p75 neurotrophin receptor and sortilin, could induce neuronal apoptosis and are implicated in the pathogenesis of various neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF), one of the most potent useful neurotrophic factors for the treatment of Parkinson’s disease (PD), is firstly synthesized as the proform (proGDNF) like other neurotrophin NGF, BDNF, and NT3. However, little is known about proGDNF expression and secretion under physiological as well as pathological states in vivo or in vitro. In this study, we investigated the expression profile and dynamic changes of proGDNF in brains of aging and PD animal models, with the interesting finding that proGDNF was a predominant form of GDNF with molecular weight of about 36 kDa by reducing and nonreducing immunoblots in adult brains and was unregulated in the aging, lipopolysaccharide (LPS), and 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) insult. We further provided direct evidence that accompanied activation of primary astrocytes as well as C6 cell line induced by LPS stimulation, proGDNF was increasingly synthesized and released as the uncleaved form in cell culture. Taken together, our results strongly suggest that proGDNF may be a biologically active protein and has specific effects on the cells close to its secreting site, and a potentially important role of proGDNF signaling in the brains, in the glia–neuronal interaction or in the pathogenesis of PD, should merit further investigation.     

Changes in Glial Cell Line-derived Neurotrophic Factor Expression in the Rostral and Caudal Stumps of the Transected Adult Rat Spinal Cord

Limited information is available regarding the role of endogenous Glial cell line-derived neurotrophic factor (GDNF) in the spinal cord following transection injury. The present study investigated the possible role of GDNF in injured spinal cords following transection injury (T₉–T₁₀) in adult rats. The locomotor function recovery of animals by the BBB (Basso, Beattie, Bresnahan) scale score showed that hindlimb support and stepping function increased gradually from 7 days post operation (dpo) to 21 dpo. However, the locomotion function in the hindlimbs decreased effectively in GDNF-antibody treated rats. GDNF immunoreactivty in neurons in the ventral horn of the rostral stump was stained strongly at 3 and 7 dpo, and in the caudal stump at 14 dpo, while immunostaining in astrocytes was also seen at all time-points after transection injury. Western blot showed that the level of GDNF protein underwent a rapid decrease at 7 dpo in both stumps, and was followed by a partial recovery at a later time-point, when compared with the sham-operated group. GDNF mRNA-positive signals were detected in neurons of the ventral horn, especially in lamina IX. No regenerative fibers from corticospinal tract can be seen in the caudal segment near the injury site using BDA tracing technique. No somatosensory evoked potentials (SEP) could be recorded throughout the experimental period as well. These findings suggested that intrinsic GDNF in the spinal cord could play an essential role in neuroplasticity. The mechanism may be that GDNF is involved in the regulation of local circuitry in transected spinal cords of adult rats.     

神经营养物质的研究进展

随着人类老龄化的进程,阿尔茨海默、帕金森等神经退行性疾病发病率日益增加.大量研究表明神经退行性疾病发病是一个多机制、多因素的复杂过程.针对其发病机理先后提出了神经细胞凋亡、氧化应激、基因遗传等多种假说.根据这些假说开展了对神经细胞有营养和保护作用物质的研究.本文综述了目前神经营养物质的研究进展.     

Glial Cell Line-Derived Neurotrophic Factor and Focal Ischemic Stroke

Neurochemical Research - Focal ischemic stroke (FIS) is a leading cause of human debilitation and death. Following the onset of a FIS, the brain experiences a series of spatiotemporal changes which...