Center of Reproduction, Development and Aging Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China.
College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Cells. 2022 Feb 14;11(4):666. doi: 10.3390/cells11040666.
Insulin-like growth factor-1 (IGF-1) and its binding proteins and receptors are widely expressed in the central nervous system (CNS), proposing IGF-1-induced neurotrophic actions in normal growth, development, and maintenance. However, while there is convincing evidence that the IGF-1 system has specific endocrine roles in the CNS, the concept is emerging that IGF-I might be also important in disorders such as ischemic stroke, brain trauma, Alzheimer's disease, epilepsy, etc., by inducing neuroprotective effects towards glutamate-mediated excitotoxic signaling pathways. Research in rodent models has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 was administered by different routes, and several clinical studies have shown safety and promise of efficacy in neurological disorders of the CNS. Focusing on the relationship between IGF-1-induced neuroprotection and glutamate-induced excitatory neurotoxicity, this review addresses the research progress in the field, intending to provide a rationale for using IGF-I clinically to confer neuroprotective therapy towards neurological diseases with glutamate excitotoxicity as a common pathological pathway.
胰岛素样生长因子-1(IGF-1)及其结合蛋白和受体在中枢神经系统(CNS)中广泛表达,提示 IGF-1 在正常生长、发育和维持中具有神经营养作用。然而,尽管有令人信服的证据表明 IGF-1 系统在 CNS 中有特定的内分泌作用,但越来越多的观点认为,IGF-1 可能在缺血性中风、脑创伤、阿尔茨海默病、癫痫等疾病中也很重要,通过诱导谷氨酸介导的兴奋毒性信号通路的神经保护作用。啮齿动物模型的研究表明,通过不同途径给予 IGF-1 可以挽救生理病理和行为异常,几项临床研究表明,IGF-1 在 CNS 神经疾病中的安全性和疗效有希望。本文聚焦于 IGF-1 诱导的神经保护与谷氨酸诱导的兴奋性神经毒性之间的关系,综述了该领域的研究进展,旨在为临床使用 IGF-1 提供依据,以对以谷氨酸兴奋毒性为共同病理途径的神经疾病进行神经保护治疗。