Réthelyi János M, Vincze Katalin, Schall Dorothea, Glennon Jeffrey, Berkel Simone
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary; Doctoral School of Mental Health Sciences, Semmelweis University, Budapest, Hungary.
Neurosci Biobehav Rev. 2023 Oct;153:105330. doi: 10.1016/j.neubiorev.2023.105330. Epub 2023 Jul 27.
Insulin and insulin-like growth factor 1 (IGF1) signalling play a central role in the development and maintenance of neurons in the brain, and human neurodevelopmental as well as neuropsychiatric disorders have been linked to impaired insulin and IGF1 signalling. This review focuses on the impairments of the insulin and IGF1 signalling cascade in the context of neurodevelopmental and neuropsychiatric disorders, based on evidence from human neuronal cell models. Clear evidence was obtained for impaired insulin and IGF1 receptor downstream signalling in neurodevelopmental disorders, while the evidence for its role in neuropsychiatric disorders was less substantial. Human neuronal model systems can greatly add to our knowledge about insulin/IGF1 signalling in the brain, its role in restoring dendritic maturity, and complement results from clinical studies and animal models. Moreover, they represent a useful model for the development of new therapeutic strategies. Further research is needed to systematically investigate the exact role of the insulin/IGF1 signalling cascades in neurodevelopmental and neuropsychiatric disorders, and to elucidate the respective therapeutic implications.
胰岛素和胰岛素样生长因子1（IGF1）信号传导在大脑神经元的发育和维持中起着核心作用，人类神经发育障碍以及神经精神疾病都与胰岛素和IGF1信号传导受损有关。基于人类神经元细胞模型的证据，本综述聚焦于神经发育障碍和神经精神疾病背景下胰岛素和IGF1信号级联的损伤。有明确证据表明神经发育障碍中胰岛素和IGF1受体下游信号传导受损，而其在神经精神疾病中作用的证据则不那么充分。人类神经元模型系统能够极大地增进我们对大脑中胰岛素/IGF1信号传导、其在恢复树突成熟中的作用的了解，并补充临床研究和动物模型的结果。此外，它们代表了开发新治疗策略的有用模型。需要进一步研究以系统地调查胰岛素/IGF1信号级联在神经发育障碍和神经精神疾病中的确切作用，并阐明各自的治疗意义。
