Skip to main content
SpringerLink
Log in
Book cover

Advances in Research on Neurodegeneration pp 261–272Cite as

Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway

  • Conference paper

Summary

Insulin-like growth factor-I (IGF-I) is a pleiotropic polypeptide with a wide range of actions in both central and peripheral nervous sytems. Over the past few years, we studied the trophic as well as neuromodulatory roles of IGF-I in the brain. Accumulated evidence indicates that IGF-I, apart from regulating growth and development, protects neurons against cell death induced by amyloidogenic derivatives, glucose or serum deprivation via the activation of intracellular pathways implicating phosphatidylinositide 3/Akt kinase, winged-helix family of transcription factor FKHRL1 phosphorylation or production of free radicals. The effects of IGF-I on neuroprotection, glucose metabolism and activity-dependent plasticity suggest the potential usefulness of this growth factor or related mimetics in the treatment of Alzheimer’s disease and other neurodegenerative disorders.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aizenman Y, de Vellis J (1987) Brain neurones develop in a serum and glial free environment: effects of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation. Brain Res 406: 32-42

    Article  PubMed  CAS  Google Scholar 

  • Araujo DM, Lapchak PA, Collier B, Chabot JG, Quirion R (1989) Insulin-like growth factor-1 (somatomedin-C) receptors in the rat brain: distribution and interaction with the hippocampal cholinergic system. Brain Res 484: 130-138

    Article  PubMed  CAS  Google Scholar 

  • Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42: 631-639

    Article  PubMed  CAS  Google Scholar 

  • Auld DS, Kar S, Quirion R (1998) ß-amyloid peptides as direct cholinergic neuromodulators: a missing link. Trends Neurosci 21: 43-49

    Article  PubMed  CAS  Google Scholar 

  • Baker J, Liu JP, Robertson EJ, Efstratiadis A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75: 73-82

    PubMed  CAS  Google Scholar 

  • Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM (1996) Des (1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol 28: 1085-1087

    Article  PubMed  CAS  Google Scholar 

  • Beilharz EJ, Bassett NS, Sirimanne ES, Williams CE, Gluckman PD (1995) Insulin-like growth factor-II is induced during wound repair following hypoxic-ischemic injury in the developing rat brain. Mol Brain Res 29: 81-91

    Article  PubMed  CAS  Google Scholar 

  • Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L, Hintz RL (1981) Somatomedin-C mediates growth hormone negative feed-back by effects on both the hypothalamus and the pituitary. Science 212: 1279-1281

    Article  PubMed  CAS  Google Scholar 

  • Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous sytem. J Cell Biol 101: 1371-1378

    Article  PubMed  CAS  Google Scholar 

  • Blair LA, Bence-Hanulec KK, Mehta S, Franke T, Kaplan D, Marshall J (1999) Akt-dependent potentiation of L channels by insulin-like growth factor-I is required for neuronal survival. J Neurosci 19: 1940-1951

    PubMed  CAS  Google Scholar 

  • Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239-259

    Article  PubMed  CAS  Google Scholar 

  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96: 857-868

    Article  PubMed  CAS  Google Scholar 

  • Busciglio J, Yeh J, Yankner BA (1993) Beta-amyloid neurotoxicity in human cortical culture is not mediated by excitotoxins. J Neurochem 61: 1565-1568

    Article  PubMed  CAS  Google Scholar 

  • Butler AA, Yakar S, Gewolb IH, Karas M, Okubo Y, LeRoith D (1998) Insulin-like growth factor-I signal transduction: at the interface between physiology and cell biology. Comp Biochem Physiol B Biochem Mol Biol 121: 19-26

    Article  PubMed  CAS  Google Scholar 

  • Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridg E, Frisch S, Reed JC (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282: 1318-1321

    Article  PubMed  CAS  Google Scholar 

  • Carson MJ, Behringer RR, Brinster RL, McMorris FA (1993) Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 10: 729-740

    Article  PubMed  CAS  Google Scholar 

  • Castro-Alamancos MA, Arevalo MA, Torres-Aleman I (1996) Involvement of protein kinase C and nitric oxide in the modulation by insulin-like growth factor-I of glutamate-induced GABA release in the cerebellum. Neuroscience 70: 843-847

    Article  PubMed  CAS  Google Scholar 

  • Clemmons DR (1998) Role of insulin-like growth factor binding proteins in controlling IGF actions. Mol Cell Endocrinol 140: 19-24

    Article  PubMed  CAS  Google Scholar 

  • Crews FT, McElhaney R, Freund G, Ballinger WE, Jr Raizada MK (1992) Insulin-like growth factor I receptor binding in brains of Alzheimer’s and alcoholic patients. J Neurochem 58: 1205-1210

    Article  PubMed  CAS  Google Scholar 

  • Daly RJ (1998) The Grb7 family of signalling proteins. Cell Signal 10: 613-618

    Article  PubMed  CAS  Google Scholar 

  • de Pablo F, de la Rosa EJ (1995) The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors. Trends Neurosci 18: 143-150

    Article  PubMed  CAS  Google Scholar 

  • Denu JM, Lohse DL, Vijayalakshmi J, Saper MA, Dixon JE (1996) Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis. Proc Natl Acad Sci USA 93: 2493-2498

    Article  PubMed  CAS  Google Scholar 

  • Doré S, Pelletier JP, DiBattista JA, Tardif G, Brazeau P, Martel-Pelletier J (1994) Human osteoarthritic chondrocytes possess an increased number of insulin-like growth factor 1 binding sites but are unresponsive to its stimulation. Posssible role of IGF-I-binding proteins. Arthritis Rheum 37: 253-263

    Article  PubMed  Google Scholar 

  • Doré S, Krieger C, Kar S, Quirion R (1996) Distribution and levels of insulin-like growth factor (IGF-I and IGF-II) and insulin receptor binding sites in the spinal cords of amyotrophic lateral sclerosis (ALS) patients. Mol Brain Res 41: 128-133

    Article  PubMed  Google Scholar 

  • Doré S, Kar S, Quirion R (1997a) IGF-I protects and rescues hippocampal neurones against ß-amyloid-and human amylin-induced toxicity. Proc Natl Acad Sci USA 94: 4772-4777

    Article  Google Scholar 

  • Doré S, Kar S, Quirion R (1997b) Presence and differential internalization of two distinct insulin-like growth factor (IGF-I and IGF-II) receptors in rat hippocampal formation. Neuroscience 78: 373-383

    Article  Google Scholar 

  • Doré S, Kar S, Quirion R (1997c) Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases. Trends Neurosci 20: 326-331

    Article  Google Scholar 

  • Doré S, Kar S, Rowe W, Quirion R (1997d) Distribution and levels of [’2s]IGF-I, [1251J1GF-II and [’2st]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats. Neuroscience 80: 1033-1040

    Article  Google Scholar 

  • Doré S, Kar S, Chabot J-G, Quirion R (1999) Impact of neonatal kainate treatment on hippocampal insulin-like growth factor receptors. Neuroscience 91: 1035-1043

    Article  PubMed  Google Scholar 

  • Drechsel DN, Hyman AA, Cobb MH, Kirschner MW (1992) Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell 3: 1141-1154

    PubMed  CAS  Google Scholar 

  • Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399: 597-601

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Cairns NJ, Crowther RA (1992) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8: 159-168

    Article  PubMed  CAS  Google Scholar 

  • Greenberg SG, Davies P (1990) A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 87: 5827-5831

    Article  PubMed  CAS  Google Scholar 

  • Guthrie KM, Nguyen T, Gall CM (1995) Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus: spatiotemporal correspondence of a trophic event with axon sprouting. J Comp Neurol 352: 147-160

    Article  PubMed  CAS  Google Scholar 

  • Harris ME, Hensley K, Butterfield DA, Leedle RA, Carney JM (1995) Direct evidence of oxidative injury produced by the Alzheimer’s beta-amyloid peptide (1-40) in cultured hippocampal neurons. Exp Neurol 131: 193-202

    Article  PubMed  CAS  Google Scholar 

  • Hong M, Lee VM (1997) Insulin and insulin-like growth factor-I regulate tau phosphorylation in cultured human neurons. J Biol Chem 272: 19547-19553

    Article  PubMed  CAS  Google Scholar 

  • Isaksson OG, Ohlsson C, Nilsson A, Isgaard J, Lindahl A (1991) Regulation of cartilage growth by growth hormone and insulin-like growth factor I. Pediatr Nephrol 5: 451-453

    Article  PubMed  CAS  Google Scholar 

  • Jafferali S, Dumont Y, Sotty F, Robitaille Y. Quirion R, Kar S (2000) Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus and cerebellum of normal human and Alzheimer’s disease brains. Synapse (in press)

    Google Scholar 

  • Johansson AG, Lindh E, Ljunghall S (1993) Growth hormone, insulin-like growth factor I, and bone: a clinical review. J Intern Med 234: 553-560

    Article  PubMed  CAS  Google Scholar 

  • Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16: 3-34

    PubMed  CAS  Google Scholar 

  • Kar S, Baccichet A, Quirion R, Poirier J (1993) Entorhinal cortex lesion induces differential responses in [1251]insulin receptor binding sites in the rat hippocampal formation. Neuroscience 55: 69-80

    Article  PubMed  CAS  Google Scholar 

  • Kar S, Seto D, Doré S, Hanisch U, Quirion R (1997) Insulin-like growth factor-I and -II differentially regulate endogenous acetylcholine release from the hippocampal formation. Proc Natl Acad Sci USA 94: 14054-14059

    Article  PubMed  CAS  Google Scholar 

  • Lackey BR, Gray SL, Henricks DM (2000) Actions and interactions of the IGF system in Alzheimer’s disease: review and hypothesis. Growth Hor IGF Res 10: 1-13

    Article  CAS  Google Scholar 

  • Lee VM, Brain BJ, Otvos L, Jr Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251: 675-678

    Article  PubMed  CAS  Google Scholar 

  • Lee WH, Javedan S, Bondy CA (1992) Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development. J Neurosci 12: 4737-4744

    PubMed  CAS  Google Scholar 

  • Lenoir D, Honegger P (1983) Insulin-like growth factors I (IGF-I) stimulates DNA synthesis in fetal rat brain cell cultures. Brain Res 283: 205-213

    PubMed  CAS  Google Scholar 

  • LeRoith D, Werner H, Beitner-Johnson D, Roberts CT (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16: 143-163 Lienhard GE (1994) Insulin. Life without the IRS. Nature 372: 128-129

    PubMed  CAS  Google Scholar 

  • Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW (1993) Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA 90: 7951-7955

    Article  PubMed  CAS  Google Scholar 

  • Maurice T, Lockhart BP, Privat A (1996) Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction. Brain Res 706: 181-193

    Article  PubMed  CAS  Google Scholar 

  • Meyerovitch J, Farfel Z, Sack J, Shechter Y (1987) Oral administration of vandate normalizes blood glucose levels in streptozotocin-treated rats. Characterization and mode of action. J Biol Chem 262: 6658-6662

    PubMed  CAS  Google Scholar 

  • Nilsson L, Sara VR, Nordberg A (1988) Insulin-like growth factor-I stimulates the release of acetylcholine from rat cortical slices. Neurosci Lett 88: 221-226

    Article  PubMed  CAS  Google Scholar 

  • Pankov YA (1999) Growth hormone and a partial mediator of its biological action, insulin-like growth factor I. Biochemistry (Moscow) 64: 1-7

    CAS  Google Scholar 

  • Price DL, Sisodia SS, Gandy SE (1995) Amyloid beta amyloidosis in Alzheimer’s disease. Curr Opin Neurol 8: 268-274

    Article  PubMed  CAS  Google Scholar 

  • Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ (1993) Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer’s disease. Proc Natl Acad Sci USA 90: 10836-10840

    Article  PubMed  CAS  Google Scholar 

  • Rotwein P, Burgess SK, Milbrandt JD, Krause JE (1988) Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci USA 85: 265-269

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (1998) The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol 8: 447-453

    Article  PubMed  CAS  Google Scholar 

  • Shemer J, Adamo M, Wilson GL, Heffez D, Zick Y, LeRoith D (1987) Insulin-like growth factor I receptors in neuronal and glial cells. Characterization and biological effects in primary culture. J Biol Chem 262: 15476-15482

    PubMed  CAS  Google Scholar 

  • Traxler P, Furet P (1999) Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol Ther 82: 195-206

    Article  PubMed  CAS  Google Scholar 

  • Venters HD, Dantzer R, Kelley KW (2000) A new concept in neurodegeneration: TNFa is a silencer of survival signals. Trends Neurosci 23: 175-180

    Article  PubMed  CAS  Google Scholar 

  • Waters SB, Chen D, Kao AW, Okada S, Holt KH, Pessin JE (1996) Insulin and epidermal growth factor receptors regulate distinct pools of Grb2-SOS in the control of Ras activation. J Biol Chem 271: 18224-18230

    Article  PubMed  CAS  Google Scholar 

  • Zhang B, Salituro G, Szalkowski D, Li Z, Zhang Y, Royo I, Vilella D, Diez MT, Pelaez F, Ruby C, Kendall RL, Mao X, Griffin P, Calaycay J, Zierath JR, Heck JV, Smith RG, Moller DE (1999) Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science 284: 974-977

    Article  PubMed  CAS  Google Scholar 

  • Zheng W-H, Kar S, Quirion R (2000a) Stimulation of protein kinase C modulates insulin-like growth factor-l-induced Akt activation in PC12 cells. J Biol Chem 275: 13377-13385

    Article  CAS  Google Scholar 

  • Zheng W-H, Kar S, Quirion R (2000b) Insulin-like growth facor-l-induced phosphorylation of the forkhead family of transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. J Biol Chem (submitted)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada

    W.-H. Zheng, S. Kar & S. Doré

  2. Douglas Hospital Research Centre, 6875, LaSalle Blvd., Verdun, Quebec, Canada, H4H 1R3

    R. Quirion

Authors
  1. W.-H. Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Kar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Doré
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Quirion
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  2. Neurodegenerative Disorders Centre, Faculty of Medicine, University Hospital, Vancouver, B.C., Canada

    D. B. Calne

  3. Schering AG Berlin, Berlin, Federal Republic of Germany

    R. Horowski

  4. Department of Neurology, Juntendo University, Tokyo, Japan

    Y. Mizuno

  5. Department of Neurology, Mount Sinai Medical Center, New York, New York, USA

    C. W. Olanow

  6. Department of Neurology, University of Innsbruck, Innsbruck, Austria

    W. Poewe

  7. Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

    M. B. H. Youdim

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Wien

About this paper

Cite this paper

Zheng, WH., Kar, S., Doré, S., Quirion, R. (2000). Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway. In: Riederer, P., et al. Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6301-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6301-6_17

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83537-1

  • Online ISBN: 978-3-7091-6301-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation