Department of Biomedical Sciences (DBS), University of Padova, 35131 Padova, Italy; Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy; Padova Neuroscience Center (PNC), 35131 Padova, Italy; Myology Center (CIR-Myo), 35131 Padova, Italy.
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA; Division of Child Neurology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Front Neuroendocrinol. 2020 Apr;57:100821. doi: 10.1016/j.yfrne.2020.100821. Epub 2020 Jan 30.
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.
胰岛素样生长因子 1（IGF-1）是一种具有多种生物学功能的肽类激素，能够调节人体的稳态和细胞的生长。IGF-1 通过激活两条主要的信号通路——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）——来促进大脑的发育、代谢和功能，并维持神经元的存活和生长。在本文中，我们将讨论 IGF-1 信号通路的一般作用和组织特异性作用。此外，我们还将全面探讨 IGF-1 在神经退行性疾病中的作用，如脊髓性肌萎缩症、肌萎缩性侧索硬化症和多聚谷氨酰胺疾病。在每种疾病中，我们都分析了 IGF-1 信号通路的紊乱、疾病蛋白被 IGF-1 信号修饰的情况，以及目前基于 IGF-1 应用的治疗策略。最后，我们强调了目前和未来在使用 IGF-1 治疗这些疾病时需要考虑的问题。
