Insulin-like growth factor binding protein-2 as a regulator of IGF actions in CNS: implications in multiple sclerosis.
Insulin-like growth factors (IGFs) are indispensable peptide hormones for proper development of the central nervous system (CNS). Because IGF-1 exhibits neuroprotective and myelinogenetic effects, it possesses therapeutic potential in treating neurodegenerative demyelinating diseases such as multiple sclerosis (MS). However, IGF actions are largely dependant on high-affinity regulatory IGF binding proteins (IGFBPs), which are likely to interfere with therapeutic attempts at elevating IGF-1 levels in the CNS. In particular, IGFBP-2 plays a dominant role in IGF regulation in the CNS and is upregulated in several pathological conditions, including MS. The question remains as to whether IGFBPs should be considered "interfering" components of IGF treatment strategies or might possibly be utilized to clinical advantage. This review discusses our current understanding of biological functions of IGFBP-2 in the CNS and its implications in the demyelinating disease MS.
Chesik
Daniel
D
Department of Neurology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. d.chesik@med.umcg.nl
De Keyser
Jacques
J
Wilczak
Nadine
N
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D016543:Central Nervous System Neoplasms / Q000378:metabolism; D003711:Demyelinating Diseases; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*
D018971:Insulin-Like Growth Factor Binding Protein 2; D008024:Ligands; D007334:Insulin-Like Growth Factor I