[Frontiers in Bioscience 14, 352-375, January 1, 2009]
IGF-IR in neuroprotection and brain tumors
Elisa Gualco1, Jin Ying Wang1, Luis Del Valle1, Katarzyna Urbanska1,2, Francesca Peruzzi1, Kamel Khalili1, Shohreh Amini1, Krzysztof Reiss1
1Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19122; 2Department of Cell Biology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland
TABLE OF CONTENTS
The IGF-IR is a multifunctional tyrosine kinase receptor involved in several biological processes including cell proliferation, differentiation, DNA repair, and cell survival. In the brain IGF-I plays a critical role during embryonic and early postnatal development. In the mature brain, IGF-I binding sites have been found in different regions of the brain, and multiple reports confirmed a strong neuroprotective action of the IGF-IR against different pro-apoptotic insults. When the IGF-IR signaling system is insufficiently deployed, either by low level of expression in elderly individuals, or by the inhibition associated with inflammatory cytokines, neuronal function and survival could be compromised. The examples of such CNS pathologies include HIV associated dementia, diabetic neuropathies, and Alzheimer's disease. On the other hand, elevated expression activity of the IGF-IR may support uncontrolled cell proliferation and protection from apoptosis. Probably the best example of the IGF-IR involvement in brain tumors is medulloblastomas in which functional cooperation between viral oncoprotein, JC virus large T-antigen, and IGF-IR has been recently established. Therefore, better understanding of the beneficial and potentially harmful aspects of the IGF-IR can be critical for the development of new clinical regimens against neurodegenerative disorders and brain tumors.