Anlar B, Sullivan K A, Feldman E L
University of Michigan, Department of Neurology, Ann Arbor, USA.
Horm Metab Res. 1999 Feb-Mar;31(2-3):120-5. doi: 10.1055/s-2007-978708.
Insulin-like growth factor-I (IGF-I), a 70-amino acid-protein structurally similar to insulin, promotes cell proliferation and differentiation in multiple tissues. Most of its effects are mediated by the Type I IGF receptor (IGF-IR), a heterotetramer that has tyrosine kinase activity and phosphorylates insulin receptor substrates (IRS-1 and 2) which leads to the activation of two downstream signaling cascades: the MAP kinase and the phosphatidylinositol 3-kinase (P3K) cascades. The growth-promoting effects of IGF-I are prominent in the nervous system, qualifying this molecule as a neurotrophin. Although the primary regulator of IGF-I expression is growth hormone (GH), the developmental expression of IGF-I in various tissues precedes that of GH, supporting an independent role of IGF-I in embryonic and fetal life [1]. This review will examine the effect of IGF-I on central nervous system (CNS) development. The specialized structure of the CNS is the product of a complex series of biological events which result from the interaction between the cells' genetic program and environmental influences. CNS development begins in the embryo with dorsal ectodermal cell proliferation to form the neural plate, and, with its closure, the neural tube, followed by the rapid division of pluripotential cells, their migration to the periphery of the neural tube, and differentiation into neural or glial cells. During the latter stages, cells form special structures such as nuclei, ganglia, cerebral cortical layers, and they also develop a network with their cytoplasmic extensions, neurites. Many more cells and connections are generated in fetal life than are found in the mature organism. This excessive production of some cell groups and neurites may compensate for tissue loss due to various injuries, and their selective elimination also constitutes an efficient way to organize the architecture of the CNS. This elimination is believed to be accomplished by apoptosis. The cells' intrinsic program for development includes the expression of various genes at different times. Environmental influences, such as extracellular matrix (ECM) molecules that attract or repel cells, afferent inputs, and target-derived diffusible molecules modify and modulate cellular behavior. IGF-I is among the molecules which affect several steps involved in development.
胰岛素样生长因子-I（IGF-I）是一种由70个氨基酸组成的蛋白质，其结构与胰岛素相似，可促进多种组织中的细胞增殖和分化。它的大部分作用是由I型IGF受体（IGF-IR）介导的，IGF-IR是一种具有酪氨酸激酶活性的异源四聚体，可使胰岛素受体底物（IRS-1和2）磷酸化，从而激活两个下游信号级联反应：丝裂原活化蛋白激酶（MAPK）级联反应和磷脂酰肌醇3-激酶（P3K）级联反应。IGF-I的促生长作用在神经系统中尤为显著，这使该分子成为一种神经营养因子。虽然IGF-I表达的主要调节因子是生长激素（GH），但IGF-I在各种组织中的发育表达先于GH，这支持了IGF-I在胚胎和胎儿期的独立作用[1]。本综述将探讨IGF-I对中枢神经系统（CNS）发育的影响。CNS的特殊结构是一系列复杂生物事件的产物，这些事件是细胞遗传程序与环境影响相互作用的结果。CNS发育始于胚胎期，背侧外胚层细胞增殖形成神经板，随着神经板闭合形成神经管，随后多能细胞迅速分裂，迁移到神经管周围，并分化为神经细胞或神经胶质细胞。在后期阶段，细胞形成特殊结构，如细胞核、神经节、大脑皮层层，它们还通过其细胞质延伸物（神经突）形成网络。胎儿期产生的细胞和连接比成熟生物体中多得多。一些细胞群和神经突的过度产生可能补偿因各种损伤导致的组织损失，而它们的选择性消除也是构建CNS结构的有效方式。据信这种消除是通过细胞凋亡完成的。细胞的内在发育程序包括在不同时间表达各种基因。环境影响，如吸引或排斥细胞的细胞外基质（ECM）分子、传入输入和靶源性可扩散分子，会改变和调节细胞行为。IGF-I是影响发育过程中多个步骤的分子之一。
