INSULIN-LIKE GROWTH-FACTORS REGULATE NEURONAL DIFFERENTIATION AND SURVIVAL

Insulin-like growth factor I (IGF-I) and IGF-II are potent trophic fac tors for motor and sensory neurons and glial cells. The actions of IGF -I and IGF-II are mediated via the IGF-I receptor (IGF-IR). IGF:IGF-IR binding activates distinct signaling cascades, which in turn mediate the trophic effects of the IGFs. We discuss three main IGF coupled eve nts: growth cone motility, long-term neurite outgrowth, and neuroprote ction. Our data suggest that IGF-I enhances growth cone motility by pr omoting reorganization of actin and activation of focal adhesion prote ins via the phosphatidylinositol-3 kinase (PI-3K) pathway. Long-term t reatment with IGF-I activates the mitogen-activated protein (MAP) kina se cascade and promotes neurite outgrowth. A separable, but likely lin ked, action of the IGFs via PI-3K is protection of neurons from apopto sis. These pleotrophic effects of IGFs suggest that this family of gro wth factors may have potential clinical utility in the treatment of ne urological disorders. (C) 1997 Academic Press.