The brain IGF system: Implications for Down syndrome

The insulin-like growth factors (IGFs) are a family of peptide hormones which regulate cellular growth, anabolism and survival via specific receptors located on the plasma membranes of their target cells. The action of the IGFs is modulated by their binding proteins which regulate their bio-availability. We have characterized the IGF genes and their protein products in the human brain. The IGFs are synthesized in the human brain throughout life, with their gene expression being regionally and developmentally regulated. The co-distribution of IGF-1 mRNA and receptors indicates an autocrine/paracrine action, whereas the distribution of IGF-2-producing cells in highly vascularized regions indicates that this peptide is important for substrate, uptake and transport. Using recombinant peptides, the neurotrophic activity of the IGFs which is medicated via the IGF-1 receptor has been established both in vitro and in vivo. The IGFs continue to be reproduced within the mature nervous system where they have an anabolic action regulating substrate uptake and cellular metabolism. The IGFs appear to be essential for the maintenance of the mature nervous system and have been implicated in neurodegenerative diseases. Disturbances in the IGF system may contribute to the brain dysfunction in Down syndrome.