Submitted on May 20, 2008
Revised on August 12, 2008
Accepted on August 15, 2008
Abnormalities of IGF-I Signaling in the Pathogenesis of Diseases of the Bone, Brain, and Feto-Placental Unit in Humans
Luigi Laviola1, Annalisa Natalicchio1, Sebastio Perrini1, and Francesco Giorgino1*
1 University of Bari
* To whom correspondence should be addressed. E-mail: f.giorgino{at}endo.uniba.it.
IGF-I action is essential for the regulation of tissue formation and remodeling, bone growth, prenatal growth, brain development, and muscle metabolism. Cellular effects of IGF-I are mediated through the IGF-I receptor, a trans-membrane tyrosine kinase, which phosphorylates intracellular substrates, resulting in the activation of multiple intracellular signaling cascades. Dysregulation of IGF-I actions due to impairment in the post-receptor signaling machinery may contribute to multiple diseases in humans. This article will review current information on IGF-I signaling and illustrate recent results demonstrating how impaired IGF-I signaling and action may contribute to the pathogenesis of human diseases, including osteoporosis, neurodegenerative disorders, and reduced fetal growth in utero.
