哺乳动物雷帕霉素靶蛋白复合物1诱导体内多巴胺能神经元的神经营养因子表达

哺乳动物雷帕霉素靶蛋白复合物1诱导体内多巴胺能神经元的神经营养因子 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf 达 韩国庆北国立大学生命科学院脑科学及工程学研究所助理教授以往研究表明哺乳动物雷帕霉素靶蛋白复合物1(mTORC1)激活由腺相关病毒[hRheb(S16H)]转导有编码人的ras基因的组成型活性形式的基因在脑（hRheb）同源富含丝氨酸的突变成组氨酸，可诱导神经营养作用，保护和修复帕金森病大鼠模型受损的多巴胺神经元，但修复的机制并不清楚。作者最新研究发现，通过病毒载体hRheb(S16H)可以极大的诱导成年多巴胺神经元体内胶质细胞源性神经营养因子和脑源性神经营养因子的表达，但此作用可被雷帕霉素，一个特定的mTORC1抑制剂显著的减弱。除了神经营养因子的诱导，作者的研究表明，使用针对的胶质细胞源性神经营养因子和脑源性神经营养因子的中和抗体，hRheb(S16H)诱导营养因子通过在PD的MPP+处理过的大鼠模型中的协同机制起到黑质纹状体多巴胺突起的保护作用。这些结果表明，特定的基因递送到多巴胺神经元中黑质，从而可以提高的mTORC1的激活，导致持续的生成神经营养因子，维持和保护成人大脑中黑质纹状体多巴胺系统。此观点发表在《中国神经再生研究（英文版）》2014年23期杂志上。 Article: "Mammalian target of rapamycin complex 1 as an inducer of neurotrophic factors in dopaminergic neurons" by Sang Ryong Kim (School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu 702-701, Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 700-842, Korea) Kim SR. Mammalian target of rapamycin complex 1 as an inducer of neurotrophic factors in dopaminergic neurons. Neural Regen Res. 2014;9(23):2036-2037. mTORC1 as an inducer of neurotrophic factors in dopaminergic neurons Mammalian target of rapamycin complex 1 (mTOR) kinase exists in two complexes, mTOR complex 1 (mTORC1) and mTORC2, which play central roles in the integration of cell growth in response to environmental conditions, including growth factors, amino acids, energy substrates, and oxygen. The researchers from Kyungpook National University have previously reported that the activation of mTORC1 by adeno-associated virus 1 (AAV1) transduction with a gene encoding the constitutively active form of human ras homolog enriched in brain (hRheb) with a mutation of serine to histidine at position 16 [hRheb(S16H)] could induce trophic effects. This resulted in the protection and restoration of DA neurons in the 6-hydroxydopamine (6-OHDA)-treated model of PD.  In addition to the induction of neurotrophic factors, our results using neutralizing antibodies against GDNF and BDNF have shown that Rheb(S16H)-induced trophic factors contribute to the protection of nigrostriatal DA projections via a synergetic mechanism in the MPP+-treated rat model of PD (Nam et al., 2014). These results suggest that a specific gene delivery to DA neurons in the SN, which can enhance the activation of mTORC1, results in the sustained production of diverse neurotrophic factors that are involved in the maintenance and protection of the nigrostriatal DA system in the adult brain. In conclusion, hRheb(S16H) has robust trophic and protective effects on nigrostriatal DA projections in the adult brain. The sustained production of GDNF and BDNF via an mTORC1-dependent pathway contributes to neuroprotection in animal models of PD (Nam et al., 2014). Similar to these effects, naringin can induce the production of GDNF in adult DA neurons, highlighting it as a therapeutic agent against neurodegeneration through mTORC1 activation (Leem et al., 2014). Although more research is necessary to support these results and to optimize treatment methods, our observations suggest that activation of mTORC1 by specific gene delivery or treatment with specific compounds can induce the production of neurotrophic factors, such as GDNF and BDNF, in DA neurons. This may be a useful strategy to protect and maintain the nigrostriatal DA system in the adult brain. Article: "Mammalian target of rapamycin complex 1 as an inducer of neurotrophic factors in dopaminergic neurons" by Sang Ryong Kim (School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu 702-701, Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 700-842, Korea) Kim SR. Mammalian target of rapamycin complex 1 as an inducer of neurotrophic factors in dopaminergic neurons. Neural Regen Res. 2014;9(23):2036-2037.