Institute of Neurobiology and Molecular Medicine, Via del Fosso di Fiorano 64/65, Rome 00143, Italy.
Cell Death Differ. 2010 Jul;17(7):1126-33. doi: 10.1038/cdd.2010.38. Epub 2010 Apr 16.
The term trophic is widely used to indicate a general pro-survival action exerted on target cells by different classes of extracellular messengers, including neurotrophins (NTs), a family of low-molecular-weight proteins whose archetypal member is the nerve growth factor (NGF). The pro-survival action exerted by NTs results from a coordinated activation of multiple metabolic pathways, some of which have only recently come to light. NGF has been shown to exert a number of different, experimentally distinguishable effects on neurons, such as survival, differentiation of target neurons, growth of nerve fibers and their guidance (tropism) toward the source of its production. We have proposed a more complete definition of the NGF trophic action that should also include its newly discovered property of inhibiting the amyloidogenic processing of amyloid precursor protein (APP), which is among the first hypothesized primary trigger of Alzheimer's disease (AD) pathogenesis. This inhibitory action appears to be mediated by a complex series of molecular events and by interactions among NGF receptors (TrkA and p75), APP processing and tau metabolic fate and function.
术语“营养”被广泛用于表示不同种类的细胞外信使(包括神经营养因子,即一组低分子量蛋白质,其典型成员是神经生长因子)对靶细胞发挥的一般促生存作用。神经营养因子发挥的促生存作用源于多种代谢途径的协调激活,其中一些途径直到最近才被发现。现已证实,神经生长因子对神经元具有多种不同的、可在实验中区分的作用,如生存、靶神经元的分化、神经纤维的生长及其向其产生源的导向(趋向性)。我们提出了对神经生长因子营养作用的更完整定义,该定义还应包括其最近发现的抑制淀粉样前体蛋白(APP)淀粉样形成加工的特性,APP 是阿尔茨海默病(AD)发病机制中最早假设的主要触发因素之一。这种抑制作用似乎是通过一系列复杂的分子事件以及神经生长因子受体(TrkA 和 p75)、APP 加工以及 tau 代谢命运和功能之间的相互作用来介导的。