The effect of insulin-like growth factors on brain myelination and their potential therapeutic application in myelination disorders.

Degenerative disorders of the cerebral white matter, leukodystrophies and demyelination diseases, are characterized by the faulty formation or excessive breakdown of myelin. Insulin-like growth factors (IGFs) promote the proliferation of oligodendrocytes as well as their myelin synthesis. IGF-I overexpressing mice show a significant increase in brain weight associated with increased myelin content. In contrast, the brains of IGF-binding protein-1 transgenic mice show a dramatic decrease in myelination. Furthermore, IGFs and IGF-binding proteins are among the factors that are induced by brain injury and have neuroprotective effects. IGFs also induce neurite growth and survival, in particular in glial cells of the peripheral nervous system. In demyelinating diseases, IGF-I may be useful for reducing myelin breakdown and promoting myelin regeneration. These observations may lead to new therapeutic applications for IGFs, for example promoting remyelination or limiting damage following brain injury.