Lewitt Moira S, Boyd Gary W
School of Health and Life Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
School of Health and Life Sciences, University of the West of Scotland, Hamilton G72 0LH, UK.
Int J Mol Sci. 2024 Apr 20;25(8):4512. doi: 10.3390/ijms25084512.
The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in , and show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.
胰岛素样生长因子（IGF）系统在中枢神经系统中具有旁分泌和内分泌作用。有证据表明，IGF信号通路在神经退行性疾病的病理生理学中发挥作用。本综述聚焦于阿尔茨海默病和帕金森病，这两种最常见的神经退行性疾病在全球范围内随着人口老龄化以及肥胖症和2型糖尿病患病率的上升而日益普遍。文中描述了用于研究神经退行性变相关分子途径的啮齿动物模型。然而，目前尚无动物模型能完全复制这些疾病。在淀粉样前体蛋白、早老素1和早老素2基因上具有三重突变的小鼠有望成为测试新型阿尔茨海默病疗法的模型。虽然因果关系尚未得到证实，但年龄、肥胖症和2型糖尿病在这两种疾病中均为危险因素这一事实，强化了IGF系统参与这些疾病的论据。IGF系统是新的治疗方法的一个有吸引力的靶点；然而，我们的认识还存在差距，首先需要加以解决。这些差距包括除了IGF-I之外，还需关注IGF系统的其他成员，包括IGF-II、IGF结合蛋白和2型IGF受体。
