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First published online on August 30, 2005
Endocrine Reviews, doi:10.1210/er.2004-0024
A more recent version of this article appeared on December 1, 2005
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THE INSULIN-LIKE GROWTH FACTOR SYSTEM AND ITS PLEIOTROPIC FUNCTIONS IN BRAIN

V C Russo*, P Gluckman, E L Feldman, and G A Werther

Murdoch Childrens Research Institute, Centre for Hormone Research, Royal Children's Hospital Parkville 3052 Victoria Australia; University of Melbourne, Dept. of Paediatrics, Parkville 3052 Victoria Australia; Liggins Institute and National Research Centre for Growth and Development; University of Auckland, New Zealand; University of Michigan, Dept. of Neurology, Ann Arbor, M, USA

* To whom correspondence should be addressed. E-mail: vince.russo{at}mcri.edu.au.

In recent years much interest has been devoted to defining the role of the insulin-like growth factor (IGF) system in the nervous system. The ubiquitous IGFs, their cell membrane receptors and their carrier binding proteins, the IGFBPs, are expressed early in the development of the nervous system and are therefore considered to play a key role in these processes. In vitro studies have demonstrated that the IGF system promotes differentiation and proliferation, and sustains survival, preventing apoptosis of neuronal and brain derived cells. Furthermore, studies of transgenic mice over-expressing components of the IGF system or mice with disruptions of the same genes have clearly shown that the IGF system plays a key role in vivo.

The availability of animal models for brain injury and neuronal degeneration has allowed the investigation of the role of IGF-I in prevention and rescue of damaged neuronal cells. These studies have thus pointed to the potential therapeutic use of IGF-I alone or in combination with other neuro-endocrine factors in the treatment of nervous system diseases.

The main aim of this review is therefore to provide an up-to-date and comprehensive analysis of the pleiotropic functions of the IGF system in the nervous tissue. To maintain focus on the IGF system, the role and functions of the insulin system in brain and neuronal cells, also important but already amply reviewed elsewhere, will be only mentioned and discussed in brief in this review.
Key words: Insulin-like growth factor • IGFBPs • brain development • neurogenesis • neuronal differentiation • brain injury • neuro-degeneration • apoptosis • neuro-protection • neuroendocrine systems • brain cancer • IGF therapy




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