Figure 3.

Overview of the potential synaptic effects of insulin-like growth factor (IGF)-1. This figure depicts the potential effects of IGF-1 on a glutamatergic synapse, which may be responsible for the positive effect of IGF-1 on synaptic transmission and prevention of cognitive decline. IGF-1 receptor signaling leads to the phosphorylation of voltage-gated calcium channels, thus increasing calcium influx and neurotransmitter release. In addition to this indirect effect, it is currently unknown whether IGF-1 also exerts a direct effect on synaptic vesicle mobilization and the core complex of SNARE proteins during exocytosis. Interestingly, at the postsynaptic site, IGF-1 may inhibit GSK3beta activity. GSK3beta is suspected of being a major factor in hyperphosphorylation of microtubule-associated protein tau. By reducing GSK3beta activity, IGF-1 could potentially prevent the formation of neurofibrillary tangles, a major pathological hallmark of Alzheimer's disease. Moreover, through PI3K activation, IGF-1 may enhance the delivery and incorporation of glutamate receptors into the dendritic spine. Further studies are required to explore the interactions between IGF-1 signaling and other kinase pathways including PKA, PKC, and CaMKII. Finally, the new insights into the molecular regulation of IGF-1 secretion must be investigated for hippocampal and cortical neurons.