Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans.
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 transmembrane tyrosine kinase that phosphorylates intracellular substrates, resulting in the activation of multiple intracellular signaling cascades. Dysregulation of IGF-I actions due to impairment in the postreceptor 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.
Laviola
Luigi
L
Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, and Metabolic Diseases, University of Bari, Bari, Italy.
Natalicchio
Annalisa
A
Perrini
Sebastio
S
Giorgino
Francesco
F
D001847:Bone Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005315:Fetal Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D010920:Placenta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010922:Placenta Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology*
D007334:Insulin-Like Growth Factor I