睫状神经营养因子突变体的克隆，表达，纯化及生物学活性的研究

发布时间：2018-04-13 11:15

本文选题：睫状神经营养因子 + 突变体　；参考：《中国药品生物制品检定所》2005年硕士论文

【摘要】：睫状神经营养因子(CNTF)是分子量为22-26KD的酸性蛋白质。因为最初是从鸡的睫状体中提取出来，并可维持鸡副交感神经节的存活而得名。它与NTF(neurotrophic factor)家族明显不同，，没有同源性，是非靶源性的营养因子，与白血病抑制因子(LIF)、白细胞介素6(IL-6)等具有相似的螺旋框架结构，因而被认为属于IL-6家族。CNTF具有多种功能，能促使多种神经细胞的存活，是第一个被发现的能维持在体和离体脊髓运动神经元的存活及突起生长的神经营养因子，CNTF还具有肌肉营养作用，在神经系统发育、分化和神经损伤修复中具有非常重要的作用。最近研究表明，睫状神经营养因子与位于丘脑部位的受体结合，能使缺乏leptin的肥胖小鼠(ob／ob mice)脂肪减少，体重降低；对于更能代表人类肥胖症实际情况的食物诱导肥胖小鼠(diet-induced obesity，DIO)模型，CNTF也能使之体重下降。与通过饮食减肥及其他的治疗方法相比，CNTF不会发生停药后过量摄入食物而引起的体重反弹。因此，CNTF具有广阔的临床开发前景，有望开发成为一种新型、高效的减肥产品。 CNTF受体在神经系统和骨骼肌中广泛存在，在运动神经系统以及与运动系统有关的部位大量表达。CNTF受体由CNTFRα、gp130、LIFRβ三部份组成，其中CNTFRα是CNTF特异性结合部位，决定哪些细胞对CNTF有反应，而gp130、LIFRβ与信号传导有关。CNTF的诸多生物学功能主要是通过激活CNTFRα，然后介导信号转导完成的。因此，通过对CNTF与CNTFRα相互作用的分子机制的研究，确定CNTF的关键
[Abstract]:Ciliary neurotrophic factor (CNTF) is an acidic protein with molecular weight of 22-26KD.It was originally extracted from the ciliary body of the chicken and can maintain the survival of the parasympathetic ganglion.It is different from NTF(neurotrophic family and has no homology. It is a non-target source nutrition factor, and has similar helical frame structure with leukemia suppressor, interleukin-6 (IL-6) and so on. Therefore, it is considered to belong to the IL-6 family. CNTF has many functions.CNTF, the first neurotrophic factor found to maintain the survival and growth of motor neurons in vivo and in vitro, also has muscular nutrition and develops in the nervous system.Differentiation and repair of nerve injury play a very important role.Recent studies have shown that ciliary neurotrophic factors combined with receptors located in the thalamus can reduce fat and weight in obese mice lacking leptin.The CNTF can also make the obese mice lose weight, which is more representative of the actual situation of human obesity.Compared with diet and other treatments, CNTF does not cause weight rebound due to excessive intake of food after withdrawal.Therefore, CNTF has a broad prospect of clinical development and is expected to become a new and efficient weight loss product.CNTF receptors are widely expressed in the nervous system and skeletal muscle. CNTF-receptors are highly expressed in the motor nervous system and motor system-related sites. CNTF-receptors are composed of three parts of CNTFR 伪 gp130 LIFR 尾, in which CNTFR 伪 is a specific binding site for CNTF, which determines which cells respond to CNTF.However, many biological functions of gp130 LIFR 尾 related to signal transduction are mainly accomplished by activating CNTFR 伪 and mediating signal transduction.Therefore, by studying the molecular mechanism of the interaction between CNTF and CNTFR 伪, the key of CNTF is determined.
【学位授予单位】：中国药品生物制品检定所
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R346

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