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脑源性神经营养因子的分子克隆与表达

Molecular cloning and expression of brain-derived neurotrophic factor.

作者信息

Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde Y A

机构信息

Max-Planck Institute for Psychiatry, Department of Neurochemistry, Planegg-Martinsried, FRG.

出版信息

Nature. 1989 Sep 14;341(6238):149-52. doi: 10.1038/341149a0.

DOI:10.1038/341149a0
PMID:2779653
Abstract

During the development of the vertebrate nervous system, many neurons depend for survival on interactions with their target cells. Specific proteins are thought to be released by the target cells and to play an essential role in these interactions. So far, only one such protein, nerve growth factor, has been fully characterized. This has been possible because of the extraordinarily (and unexplained) large quantities of this protein in some adult tissues that are of no relevance to the developing nervous system. Whereas the dependency of many neurons on their target cells for normal development, and the restricted neuronal specificity of nerve growth factor have long suggested the existence of other such proteins, their low abundance has rendered their characterization difficult. Here we report the full primary structure of brain-derived neurotrophic factor. This very rare protein is known to promote the survival of neuronal populations that are all located either in the central nervous system or directly connected with it. The messenger RNA for brain-derived neurotrophic factor was found predominantly in the central nervous system, and the sequence of the protein indicates that it is structurally related to nerve growth factor. These results establish that these two neurotrophic factors are related both functionally and structurally.

摘要

在脊椎动物神经系统发育过程中,许多神经元的存活依赖于与靶细胞的相互作用。人们认为靶细胞会释放特定蛋白质,这些蛋白质在这些相互作用中起着至关重要的作用。到目前为止,只有一种这样的蛋白质——神经生长因子——得到了充分的表征。这之所以成为可能,是因为在一些与发育中的神经系统无关的成年组织中,这种蛋白质的含量异常(且无法解释)地高。虽然许多神经元正常发育对靶细胞的依赖性,以及神经生长因子有限的神经元特异性长期以来表明存在其他此类蛋白质,但它们的低丰度使其表征变得困难。在此我们报告脑源性神经营养因子的完整一级结构。这种非常罕见的蛋白质已知能促进全部位于中枢神经系统或与之直接相连的神经元群体的存活。脑源性神经营养因子的信使核糖核酸主要在中枢神经系统中被发现,并且该蛋白质的序列表明它在结构上与神经生长因子相关。这些结果表明这两种神经营养因子在功能和结构上均相关。

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