Biosynthesis and Biological Role of Insulin-like Growth Factors in the Nervous System
The critical period for the growth and differentiation of the nervous system occurs during fetal and early postsnatal life. During this time there is rapid proliferation of the stem cells, migration and differentiation into neurones and glia, and the establishment of synaptic connections as well as the selective death of specific cells. Disturbance in this growth process can often result in permanent and irreversible defects in CNS structure and influence the consequent function of the brain. Whilst some plasticity is maintained within the nervous system throughout life, the developing glial cells, and especially the neurones which cease to proliferate after their differentiation, are particularly vulnerable during this early period of rapid growth. Understanding the mechanisms which regulate the proliferation and differentiation of the neurones and glia is thus of foremost importance in ensuring the optimal development of the CNS and its later function. In recent years it has become increasingly evident that these processes are regulated by the complex interaction of several growth factors, such as fibroblast growth factor (FGF), nerve growth factor (NGF) and the insulin-like growth factors (IGFs). The present paper will focus on the role of the IGFs. Any consideration of the biological role of the IGFs must also include that of their binding proteins (IGFBPs) and receptors (IGF-1R and IGF-2R).
KeywordsNerve Growth Factor Human Fetal Brain Nerve Growth Factor Binding Central Nervous System Precursor Glucose Transporter Gene Expression
Unable to display preview. Download preview PDF.
- 1.Ayer-LeLievre C, Ståhlbom PA, Sara VR (1991) Expression of IGF-1 and IGF-2 mRNA in the brain and cranio-facial region of the rat fetus. Development 111:105–115.Google Scholar
- 12.Hepler JE, Lund PK (1990) Molecular biology of the insulin-like growth factors. Relevance to nervous system function. In: Bazan N (ed) Molecular neurobiology. Human, New york, pp 93–127.Google Scholar
- 28.Sara VR, Carlsson-Skwirut C, Bergman T, Jörnvall H, Roberts PJ, Crawford M, Nilsson-Håkansson L, Civalero I, Nordberg A (1989) Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide. Biochem Biophys Res Commun 165:766–771.PubMedCrossRefGoogle Scholar