Synergistic Trophic Actions on Rat Basal Forebrain Neurons Revealed by a Synthetic NGF/BDNF Chimaeric Molecule
Synergistic Trophic Actions on Rat Basal Forebrain Neurons Revealed by a Synthetic NGF/BDNF Chimaeric Molecule
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合成 NGF/BDNF 嵌合分子对大鼠基底前脑神经元的协同营养作用
DOI：
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发表时间：
1995
影响因子：
3.4
通讯作者：
Carlos F. Ibáñez
中科院分区：
文献类型：
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作者：
Wilma J. Friedman;Ira B. Black;Helena Persson;Carlos F. Ibáñez
基底前脑胆碱能神经元在阿尔茨海默病中退化，对多种营养因子有反应，包括神经营养因子、神经生长因子（NGF）和脑源性神经营养因子（BDNF）。这种双重反应促使我们研究了一种合成嵌合分子的作用，该分子含有NGF和BDNF的活性结构域。NGF/BDNF嵌合因子表现出协同作用，在提高培养的游离基底前脑胆碱能神经元的存活率方面比野生型BDNF强100倍。这种效果显然是由于BDNF/NGF的协同作用，因为两种野生型营养因子的添加同时复制了嵌合体的效果。对两种因子均有反应的神经元具有选择性协同作用；黑质多巴胺能神经元对BDNF有反应，而对NGF没有反应。因此，嵌合因子揭示了一种通常可能发生在大脑中的协同作用，并构成了一种潜在的新型治疗剂，其效力比天然存在的单个营养素更强。
Basal forebrain cholinergic neurons, which degenerate in Alzheimer's disease, respond to multiple trophic factors, including the neurotrophins, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF). This dual responsiveness prompted us to investigate the effects of a synthetic chimaeric molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic actions, and was 100‐fold more potent than wild‐type BDNF in enhancing survival of cultured dissociated basal forebrain cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy, since addition of the two wild‐type trophins simultaneously reproduced the effect of the chimaera. Synergy was selective for neurons which respond to both factors; substantia nigra dopaminergic neurons, which respond to BDNF but not NGF, exhibited no potentiation. The chimaeric factor thus revealed a synergy that may normally occur in the brain, and constitutes a potentially novel therapeutic agent with greater potency than naturally occurring individual trophins.
DOI：
10.1073/pnas.83.23.9231
发表时间：
1986-12-01
影响因子：
11.1
作者：
WILLIAMS, LR;VARON, S;GAGE, FH
通讯作者：
GAGE, FH
影响因子：
56.9
作者：
KAPLAN, DR;HEMPSTEAD, BL;PARADA, LF
通讯作者：
PARADA, LF
DOI：
10.1073/pnas.88.3.961
发表时间：
1991-02-01
影响因子：
11.1
作者：
KNUSEL, B;WINSLOW, JW;HEFTI, F
通讯作者：
HEFTI, F