Friedman W J, Black I B, Persson H, Ibáñez C F
Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, Piscataway, USA.
Eur J Neurosci. 1995 Apr 1;7(4):656-62. doi: 10.1111/j.1460-9568.1995.tb00669.x.
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.
基底前脑胆碱能神经元在阿尔茨海默病中会发生退化，它们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一种包含NGF和BDNF活性结构域的合成嵌合分子的作用。NGF/BDNF嵌合因子表现出协同作用，在提高培养的离体基底前脑胆碱能神经元的存活率方面，其效力比野生型BDNF强100倍。这种效应显然是由于真正的BDNF/NGF协同作用，因为同时添加两种野生型营养因子可重现嵌合体的效应。协同作用对两种因子都有反应的神经元具有选择性；黑质多巴胺能神经元对BDNF有反应，但对NGF无反应，未表现出增强作用。因此，这种嵌合因子揭示了一种可能在大脑中正常发生的协同作用，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因子更强。
