The role of insulin/IGF1 signalling in neurodevelopmental and neuropsychiatric disorders - Evidence from human neuronal cell models

János M Réthelyi; Katalin Vincze; Dorothea Schall; Jeffrey Glennon; Simone Berkel

doi:10.1016/j.neubiorev.2023.105330

The role of insulin/IGF1 signalling in neurodevelopmental and neuropsychiatric disorders - Evidence from human neuronal cell models

Neurosci Biobehav Rev. 2023 Oct:153:105330. doi: 10.1016/j.neubiorev.2023.105330. Epub 2023 Jul 27.

Authors

János M Réthelyi¹, Katalin Vincze², Dorothea Schall³, Jeffrey Glennon⁴, Simone Berkel⁵

Affiliations

¹ Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
² Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary; Doctoral School of Mental Health Sciences, Semmelweis University, Budapest, Hungary.
³ Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
⁴ Conway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
⁵ Institute of Human Genetics, Heidelberg University, Heidelberg, Germany; Interdisciplinary Centre of Neurosciences (IZN), Heidelberg University, Germany. Electronic address: Simone.Berkel@med.uni-heidelberg.de.

PMID: 37516219
DOI: 10.1016/j.neubiorev.2023.105330

Abstract

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.

Keywords: AKT; Disease modelling; Embryonic stem cells; IGF1; Induced pluripotent stem cells; Insulin; MAPK-ERK; MTOR; Neurodevelopmental disorders; Neuronal cell models; Neuropsychiatric disorders; RAS.

Publication types

Review