Review article
The effect of insulin-like growth factors on brain myelination and their potential therapeutic application in myelination disorders

https://doi.org/10.1016/S1090-3798(97)80039-6Get rights and content

Degenerative disorders of the cerebral white matter, leukodystrophies and demyelination diseases, are characterized by the faulty formation or excessive breakdown of myelin. Insulin-like growth factors (IGFs) promote the proliferation of oligodendrocytes as well as their myelin synthesis. IGF-I overexpressing mice show a significant increase in brain weight associated with increased myelin content. In contrast, the brains of IGF-binding protein-1 transgenic mice show a dramatic decrease in myelination. Furthermore, IGFs and IGF-binding proteins are among the factors that are induced by brain injury and have neuroprotective effects. IGFs also induce neurite growth and survival, in particular in glial cells of the peripheral nervous system. In demyelinating diseases, IGF-I may be useful for reducing myelin breakdown and promoting myelin regeneration. These observations may lead to new therapeutic applications for IGFs, for example promoting remyelination or limiting damage following brain injury.

References (143)

  • ShemerJ et al.

    Insulin-like growth factor I receptors in neuronal and glial cells

    J Biol Chem

    (1987)
  • MastersBA et al.

    Insulin-like growth factor I (IGF-I) receptors and IGF-I action in oligodendrocytes from rat brains

    Regul Pept

    (1991)
  • BarresBA et al.

    Cell death and control of cell survival in the oligodendrocyte lineage

    Cell

    (1992)
  • Torres-AlemanI et al.

    Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture

    Neuroscience

    (1990)
  • Garcia-SeguraLM et al.

    Localization of insulin-like growth factor I (IGF-I)-like immunoreactivity in the developing and adult rat brain

    Brain Res

    (1991)
  • WigginsRC

    Myelin development and nutritional insufficiency

    Brain Res

    (1982)
  • GreenfieldS et al.

    Evidence for defective incorporation of proteins in myelin of the quaking mutant mouse

    Brain Res

    (1977)
  • MacklinWB et al.

    An AG → GG transition at a splice site in the myelin proteolipid protein gene in jimpy mice results in the removal of an exon

    FEBS Lett

    (1987)
  • BakerJ et al.

    Role of the insulin-like growth factors in embryonic and postnatal growth

    Cell

    (1993)
  • LiuJP et al.

    Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type I IGF receptor (Igf1r)

    Cell

    (1993)
  • BeckKD et al.

    Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons

    Neuron

    (1995)
  • CarsonMJ et al.

    Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice

    Neuron

    (1993)
  • YeP et al.

    Insulin-like growth factor-I influences the initiation of myelination: studies of the anterior commissure of transgenic mice

    Neurosci Lett

    (1995)
  • D'ErcoleAJ et al.

    Human insulin-like growth factor binding protein-1 (hIGFBP-1) transgenic mice: insights into hIGFBP-1 regulation and actions

    Prog Growth Factor Res

    (1995)
  • MurphyLJ et al.

    Phenotypic manifestations of insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 overexpression in transgenic mice

    Progr Growth Factor Res

    (1995)
  • PhillipsLS et al.

    Nutritional regulation of somatomedin

    Am J Clin Nutr

    (1979)
  • ThamA et al.

    Circulating levels of insulin-like growth factors I & II and somatomedin B in alcoholic patients

    Psych Res

    (1986)
  • SaraVR et al.

    Somatomedins in aging and dementia disorders of the Alzheimer type

    Neurobiol Aging

    (1982)
  • LeeWH et al.

    Insulin-like growth factors in the response to cerebral ischemia

    Mol Cell Neurosci

    (1992)
  • GluckmanPD et al.

    A role for IGF-I in the rescue of CNS neurons following hypoxic-ischemic injury

    Biochem Biophys Res Commun

    (1992)
  • Garcia-EstradaJ et al.

    Expression of insulin-like growth factor-I by astrocytes in responses to injury

    Brain Res

    (1992)
  • GencicS et al.

    Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein

    Am J Hum Genet

    (1989)
  • McKhannGM

    Multiple sclerosis

    Ann Rev Neurosci

    (1982)
  • Ffrench-ConstantC et al.

    The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination

    Nature

    (1986)
  • RaffMC

    Glial cell diversification in the rat optic nerve

    Science

    (1989)
  • BarresBA et al.

    Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons

    Nature

    (1993)
  • SaraVR

    The role of the insulin-like growth factors in the nervous system

  • SaraVR et al.

    The biological role of truncated insulin-like growth factor-1 and the tripeptide GPE in the central nervous system

  • SaraVR et al.

    nsulin-like growth factors in the central nervous system: biosynthesis and biological role

  • BondyCA

    Transient IGF-I gene expression during the maturation of functionally related central projec-tion neurons

    Neuroscience

    (1991)
  • BondyCA et al.

    Cellular pattern of type-1 insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II

    Neuroscience

    (1992)
  • HeplerJE et al.

    Molecular biology of the insulin-like growth factors: relevance to nervous system function

    Molec Neurobiol

    (1990)
  • BondyCA et al.

    Patterns of insulin-like growth factor and IGF receptor gene expression in the brain

    Ann NY Acad Sci

    (1993)
  • ZumkellerW et al.

    Expression and synthesis of insulin-like growth factor (IGF)-I,-II and their receptors in human glioma cell lines

    Int J Oncol

    (1996)
  • LesniakMA et al.

    Receptors for insulin-like growth factors I and II: autoradiographic localization in rat brain and comparison to receptors for insulin

    Endocrinology

    (1988)
  • MendelsohnLG et al.

    Autoradiographic localization of insulin-like growth factor n receptors in cerebellar cortex of weaver and Purkinje cell degeneration mutant mice

    Brain Res

    (1988)
  • JonesJI et al.

    Insulin-like growth factor binding protein-1 stimulates cell migration and binds to the α5βN1 integrin by means of its Arg-Gly-Asp sequence

  • JonesJI et al.

    Insulin-like growth factors and their binding protein: biological actions

    Endocrin Rev

    (1995)
  • MüllerD et al.

    Demonstration of membrane-bound insulin-like growth factorbinding proteins in human glioma cell lines

    Int J Oncol

    (1996)
  • BondyCA et al.

    Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I expression during brain development

    J Neurosci

    (1993)
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      The therapeutic potential of insulin-like growth factor-1 (IGF-1) in the treatment of demyelinating conditions has been previously investigated (Komoly et al., 1992; Mason et al., 2000a,b, 2003, Yao et al., 1995; Ye et al., 2002), yet a role for IGF-1 protection in the treatment of GLD has not been demonstrated. A number of studies have shown that IGF-1 accelerates the differentiation of OL precursors into mature OL, and it prevents apoptotic cell death in cells having the IGF-1 receptor (IGF-1R) (Dubois-Dalcq and Murray, 2000; Mason et al., 2003; Mozell and McMorris, 1988; Zumkeller, 1997). IGF-1R-containing cells are widely present in the brain, and they play an important role in the growth, development and survival of the nervous system.

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