Fig. 2

Schematic image on molecular actions of IGF-1 in CNS cells. A Blood–brain barrier (BBB)/choroid plexus (CP) and glucose homeostasis in astrocytes: IGF-1 binds to the astrocytic cell membrane's IGF-1 receptors, activates the PI3K/Akt pathway, and recruits the GLUT transporters, which then begins the uptake of glucose into the cell via GLUT transporters. B Neuroinflammation caused by microglia: When IGF-1 binds, it stimulates the polarization of the macrophages via TLR4 increasing the production of IL-1β, TNF-α, iNOS, and iba-1 while decreasing ROS and activating NF-κB/NLRP3 signaling. C PI3K/Akt/mTOR/NF-κB/CREB/MAPK signaling regulation in neurons: The PI3K/Akt signaling cascades are initiated when IGF- binds, phosphorylating the GSK, NF-κB, Bad, Caspase 9, and FOXO proteins. These additional phosphorylation result in the nuclear phosphorylation of c-fos and Bcl2, which prevents apoptosis, promotes axon development, and enhances neural plasticity. D Regulation of mitogenesis in oligodendrocytes and myelination in Schwann cells: In oligodendrocytes, IGF-1 inhibits the caspase-2 activity, shortening the G1/S cell cycle transition. In Schwann cells, IGF-1 facilitates myelination via increasing the myelinated proteins such as PLP, MBP, and NDF. E Regulation of ionic channels, synaptic function, and neurotransmitter release: IGF-1 regulates the Na⁺/Ca²⁺/K⁺ channels to increase the Ca²⁺ influx and maintain the Na⁺ concentration. In neurotransmitters, IGF-1 activates the NMDAR/KAR/AMPA receptors which regulate the acetylcholine, GABA, glutamate, and dopamine synthesis and release