Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions

Insulin-like growth factor-1 (IGF-1), a pleiotropic polypeptide, plays an essential role in CNS development and maturation. Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone that regulates blood glucose levels and fatty acid oxidation in the brain. GLP-1 also exhibits similar functions and growth factor-like prop-erties to IGF-1, which is likely how it exerts its neuroprotective effects. Recent preclinical and clinical evidence indicate that IGF-1 and GLP-1, apart from regulating growth and development, prevent neuronal death mediated by amyloidogenesis, cerebral glucose deprivation, neuroinflammation and apoptosis through modulation of PI3/ Akt kinase, mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK/ERK). IGF-1 resistance and GLP-1 deficiency impair protective cellular signaling mechanisms, contributing to the progression of neurodegenerative diseases. Over the past decades, IGF-1 and GLP-1 have emerged as an essential component of the neuronal system and as potential therapeutic targets for several neurodegenerative and neuropsychiatric dysfunctions. There is substantial evidence that IGF-1 and GLP-1 analogues penetrate the blood-brain barrier (BBB) and exhibit neuroprotective functions, including synaptic formation, neuronal plasticity, protein synthesis, and autophagy. Conclusively, this review represents the therapeutic potential of IGF-1 and GLP-1 signaling target activators in ameliorating neurological disorders.

Automated summary

Insulin-like growth factor-1 (IGF-1) and glucagon-like peptide-1 (GLP-1) play crucial roles in CNS development and protection. They prevent neuronal death and promote neuronal function through modulation of various cellular signaling pathways, making them potential therapeutic targets for neurodegenerative diseases.