The pleiotropic peptide insulin-like growth factor 1 (IGF-I) regulates human body homeostasis and cell growth. IGF-I activates two major signaling pathways, namely phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Ras/extracellular signal-regulated kinase (ERK), which contribute to brain development, metabolism and function as well as to neuronal maintenance and survival. In this review, we discuss the general and tissue-specific effects of the IGF-I pathways. In addition, we present a comprehensive overview examining the role of IGF-I in neurodegenerative diseases, such as spinal and muscular atrophy, amyotrophic lateral sclerosis, and polyglutamine diseases. In each disease, we analyze the disturbances of the IGF-I pathway, the modification of the disease protein by IGF-I signaling, and the therapeutic strategies based on the use of IGF-I developed to date. Lastly, we highlight present and future considerations in the use of IGF-I for the treatment of these disorders.

中文翻译：

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运动神经元和多聚谷氨酰胺疾病中的胰岛素样生长因子 1 信号：从分子发病机制到治疗观点

多效性肽类胰岛素生长因子 1 (IGF-I) 调节人体稳态和细胞生长。IGF-I 激活两条主要信号通路，即磷酸肌醇 3-激酶 (PI3K)/蛋白激酶 B (PKB/Akt) 和 Ras/细胞外信号调节激酶 (ERK)，它们也有助于大脑发育、代谢和功能关于神经元的维持和存活。在这篇综述中，我们讨论了 IGF-I 通路的一般和组织特异性作用。此外，我们全面概述了 IGF-I 在神经退行性疾病中的作用，如脊髓和肌肉萎缩、肌萎缩侧索硬化和多聚谷氨酰胺疾病。在每种疾病中，我们分析 IGF-I 通路的紊乱，IGF-I 信号传导对疾病蛋白质的修饰，以及迄今为止开发的基于使用 IGF-I 的治疗策略。最后，我们强调了使用 IGF-I 治疗这些疾病的当前和未来的考虑。