Neurotrophins and their Receptors
Neurotrophins and their Receptors
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神经营养素及其受体
DOI：
--
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
L. Olson
中科院分区：
文献类型：
--
作者：
H. Persson;P. Ernfors;C. Ibáñez;F. Hallböök;W. Friedman;J. Merlio;O. Lindvall;J. Bengzon;N. Lindefors;T. Ebendal;L. Olson
哺乳动物神经系统的发育和维持需要神经营养因子。神经生长因子 (NGF) 是表征最为充分的神经营养因子，最近被证明是结构相关蛋白家族的一员，该家族还包括脑源性神经营养因子 (BDNF)、神经营养蛋白-3 (NT-3) 和神经营养蛋白-4 (NT-4)。对代表性脊椎动物群体中这些因子（神经营养素）的进化研究表明，从鱼类到哺乳动物，这四个因子高度保守。构建嵌合分子，其中来自 BDNF 的序列的不同组合取代了 NGF 中的相应序列。对此类分子的生物活性的测定表明，这两种蛋白质的生物特异性是通过这两种分子之间不同的一组序列的特定组合获得的。在大脑中，最高水平的 NGF、BDNF 和 NT-3 mRNA 存在于海马体中，它们在一组独特的神经元中表达。在出生后大脑发育过程中，BDNF 和 NT-3 mRNA 都会在某些大脑区域短暂表达，这表明大脑发育过程中的营养相互作用是一种动态现象，可能会随着个体发育的不同阶段而改变。大脑中 NGF 和 BDNF mRNA 的表达似乎受到神经元活动的调节，并且这些 mRNA 的水平在癫痫发作、脑缺血和低血糖昏迷后显示出显着且短暂的增加。 NGF 和 BDNF mRNA 的增加似乎是通过海马体内谷氨酸激活 AMPA 受体的释放以及细胞内钙水平的升高介导的。原癌基因 trkB 是高亲和力 BDNF 受体的重要组成部分，也在海马体中表达，其在空间和时间上的调节方式与 BDNF 类似。这些数据表明 BDNF 及其受体可以以旁分泌/自分泌的方式在点燃相关的神经可塑性以及缺血和低血糖损伤后的神经元保护中发挥作用。表达高水平四种神经营养素的转基因细胞已被建立并用于植入大鼠大脑中，以识别体内对这些因子做出反应的细胞。使用这种方法，NGF 已被证明可以对大脑中的胆碱能神经元进行营养刺激。
Development and maintenance of the mammalian nervous system require neurotrophic factors. The most well-characterizied neurotrophic factor, nerve growth factor (NGF), has recently been shown to be a member of a family of structurally related proteins that also includes brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4). An evolutionary study of these factors (neurotrophins) in representative groups of vertebrates showed that the four factors are highly conserved from fishes to mammals. Chimeric molecules were contructed where different combinations of sequences from BDNF replaced the corresponding sequences in NGF. Assays for biological activity of such molecules showed that the biological specificities of the two proteins are obtained by specific combinations of a set of sequences that differ between the two molecules. In the brain, the highest levels of NGF, BDNF and NT-3 mRNAs are found within the hippocampus, where they are expressed in a unique set of neurons. Both BDNF and NT-3 mRNAs are transiently expressed in some brain regions during postnatal brain development, suggesting that trophic interactions during brain development are a dynamic phenomenon which may alter with various stages of ontogeny. Expression of NGF and BDNF mRNAs in the brain appears to be regulated by neuronal activity, and the levels of these mRNAs show a marked and transient increase following epileptic seizures, cerebral ischemia and hypoglycemic coma. The increases of NGF and BDNF mRNAs appear to be mediated via a release of glutamate activating AMPA receptors within the hippocampus, as well as a rise in intracellular calcium levels. The protooncogene trkB, an essential component of the high-affinity BDNF receptor, is also expressed in the hippocampus, where it is spatially and temporally regulated in a manner similar to BDNF. These data suggest that BDNF and its receptor could, in a paracrine/autocrine fashion, play a role in kindling-associated neural plasticity and in neuronal protection following ischemic and hypoglycemic insults. Genetically modified cells that express high levels of the four neurotrophins have been established and used for implantation into the rat brain to identify cells that respond to these factors in vivo. Using this approach, NGF has been shown to expert a trophic stimulation for cholinergic neurons in the brain.
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影响因子：
56.9
作者：
SUTULA, T;HE, XX;SCOTT, G
通讯作者：
SCOTT, G
产生重组神经生长因子的细胞系可引起内在和移植的中枢胆碱能神经元的生长反应。
DOI：
10.1073/pnas.86.12.4756
发表时间：
1989
影响因子：
11.1
作者：
Ernfors,P;Ebendal,T;Olson,L;Mouton,P;Strömberg,I;Persson,H
通讯作者：
Persson,H
影响因子：
56.9
作者：
KAPLAN, DR;HEMPSTEAD, BL;PARADA, LF
通讯作者：
PARADA, LF
DOI：
10.1073/pnas.89.2.648
发表时间：
1992-01-15
影响因子：
11.1
作者：
LINDVALL, O;ERNFORS, P;PERSSON, H
通讯作者：
PERSSON, H
影响因子：
56.9
作者：
GALL, CM;ISACKSON, PJ
通讯作者：
ISACKSON, PJ