Bondy Carolyn A, Cheng Clara M
Developmental Endocrinology Branch, National Institute of Child Health & Human Development/NIH, Bldg. 10/10N262, 10 Center Drive, Bethesda, MD 20892, USA.
Eur J Pharmacol. 2004 Apr 19;490(1-3):25-31. doi: 10.1016/j.ejphar.2004.02.042.
The homologous insulin and insulin-like growth factor (IGF) receptors are both expressed in the brain, in overlapping but distinct neuroanatomical patterns. In contrast to insulin, IGF1 is also highly expressed within the brain and is essential for normal brain development. IGF1 promotes projection neuron growth, dendritic arborization and synaptogenesis. IGF1 acts in an autocrine and/or paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3K)/Akt, also known as protein kinase B (PKB)/glycogen synthase kinase 3beta (GSK3beta) pathways similar to insulin signaling in peripheral tissues. IGF1 promotes neuronal survival during normal brain development mainly in hippocampal and olfactory systems that depend on postnatal neurogenesis. IGF1's anabolic and neuroprotective roles may be coordinated by inhibition of GSK3beta. The identification of GSK3beta as a major target of brain IGF1 signaling provides a unifying pathway for IGF1's well-established anabolic and anti-apoptotic functions, with IGF1-induced inhibition of GSK3beta triggering multifaceted anabolic and neuroprotective effects.
同源的胰岛素和胰岛素样生长因子（IGF）受体均在大脑中表达，呈现出重叠但又不同的神经解剖学模式。与胰岛素不同，IGF1在大脑中也高度表达，并且对正常的大脑发育至关重要。IGF1促进投射神经元生长、树突分支形成和突触发生。IGF1以自分泌和/或旁分泌的方式发挥作用，利用磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt），也称为蛋白激酶B（PKB）/糖原合酶激酶3β（GSK3β）途径来促进葡萄糖利用，这类似于外周组织中的胰岛素信号传导。在正常大脑发育过程中，IGF1主要在依赖于出生后神经发生的海马和嗅觉系统中促进神经元存活。IGF1的合成代谢和神经保护作用可能通过抑制GSK3β来协调。将GSK3β鉴定为大脑IGF1信号传导的主要靶点，为IGF1既定的合成代谢和抗凋亡功能提供了一条统一的途径，IGF1诱导的GSK3β抑制触发了多方面的合成代谢和神经保护作用。
