Insulin-like growth factors in the brain and their potential clinical implications

Insulin and insulin-like growth factors (IGFs) including IGF1 and IGF2 are members of the insulin-like peptide superfamily and have an important role in development, cell differentiation, plasticity, and survival of the nervous system. These insulin-like peptides act at several receptors that initiate downstream phosphorylation cascades that in turn regulate transcription, synaptic maturation, and apoptosis. In the adult brain, insulin and IGF1 act as circulating signals that reach the CNS by crossing the blood–brain barrier (BBB) or the blood–CSF barrier; IGF1 and IGF2 also act as paracrine signals released from all neural cells. The bioavailability of IGF1 and IGF2 is regulated by their binding to IGF binding proteins (IGFBPs). Insulin-like peptides participate in neuroprotection and may have an important role in the pathophysiology of several neurologic disorders and as potential therapeutic targets for these conditions. The insulin-like peptides, their receptors, effects in the nervous system, and potential clinical correlations have been the subject of several recent reviews.1–6 AD= : Alzheimer disease; ALS= : amyotrophic lateral sclerosis; AKT= : protein kinase B; AMPA= : α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid; BBB= : blood–brain barrier; ERK= : extracellular signal-related kinase; GH= : growth hormone; GS3K= : glycogen synthase 3 kinase; IGF= : insulin-like growth factor; IGF1R= : IGF1 receptor; IGF2R= : IGF2 receptor; IGFBP= : insulin-like growth factor binding protein; IRS= : insulin receptor substrate; LRP= : lipoprotein receptor-related protein; LTD= : long-term depression; LTP= : long-term potentiation; M6P= : mannose-6 phosphate; NMDA= : N-methyl-d-aspartate; PI3K= : phosphoinositide 3-kinase