title: Insulin-like growth factors regulate neuronal differentiation and survival.
abstract: Insulin-like growth factor I (IGF-I) and IGF-II are potent trophic factors 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 events: growth cone motility, long-term neurite outgrowth, and neuroprotection. Our data suggest that IGF-I enhances growth cone motility by promoting reorganization of actin and activation of focal adhesion proteins via the phosphatidylinositol-3 kinase (Pl-3K) pathway. Long-term treatment with IGF-I activates the mitogen-activated protein (MAP) kinase cascade and promotes neurite outgrowth. A separable, but likely linked, action of the IGFs via Pl-3K is protection of neurons from apoptosis. These pleotrophic effects of IGFs suggest that this family of growth factors may have potential clinical utility in the treatment of neurological disorders.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor 48109, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Feldman
authors.forename: K A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: B
authors.initials: B
authors.lastname: Kim
authors.forename: J W
authors.initials: JW
authors.lastname: Russell
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D013002:Somatomedins / Q000502:physiology*
chemical_list: D013002:Somatomedins