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Growth hormone/insulin-like growth factor I axis in neurodegenerative diseases

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Abstract

Neurodegenerative diseases (ND) are a group of heterogeneous disorders characterized by unknown etiology, subtle onset, and progressive involvement of neuronal systems leading to degeneration and dysfunction. They represent a challenge for basic science and clinical medicine because of increasing prevalence, social cost, complex biochemistry and pathology, and lack of mechanism-based treatments. Endocrine modifications may accompany the progression of ND, due to the intimate connections between central nervous and endocrine systems. Reported data on endocrine changes in different ND have often been non-conclusive or conflicting. GH/IGF-I axis is involved in the regulation of brain growth, development, and metabolism. Dysfunctions in GH/IGF-I axis in most of ND are therefore reviewed. Whether GH deficiency, when present, may act as a contributory factor in the pathogenesis of these diseases, or might represent a consequence of it is presently unknown. A thorough effort in investigating every possible involvement of GH/IGF-I axis is warranted, in the light of future possible therapeutic strategies.

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References

  1. Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect 2005, 113: 1250–6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Yamawaki M, Kusumi M, Kowa H, Nakashima K. Changes in prevalence and incidence of Parkinson’s disease in Japan during a quarter of a century. Neuroepidemiology 2009, 32: 263–9.

    Article  PubMed  Google Scholar 

  3. Puglielli L. Aging of the brain, neurotrophin signaling, and Alzheimer’s disease: is IGF1-R the common culprit? Neurobiol Aging 2008, 29: 795–811.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Adams RD, Victor M. Principle of Neurology. 3rd ed. New York: McGraw Hill. 1985, 859–901.

    Google Scholar 

  5. Rogaeva E, Kawarai T, George-Hyslop PS. Genetic complexity of Alzheimer’s disease: successes and challenges. J Alzheimers Dis 2006, 9: 381–7.

    PubMed  CAS  Google Scholar 

  6. Tan EK, Skipper LM. Pathogenic mutations in Parkinson disease. Hum Mutat 2007, 28: 641–53.

    Article  PubMed  CAS  Google Scholar 

  7. Rothstein JD. Current hypotheses for underlying biology of amyotrophic lateral sclerosis. Ann Neurol 2009, 65: S3–9.

    Article  PubMed  CAS  Google Scholar 

  8. Seelaar H, Kamphorst W, Rosso SM, et al. Distinct genetic forms of frontotemporal dementia. Neurology 2008, 71: 1216–7.

    Article  Google Scholar 

  9. Winklhofer KF, Tatzelt J, Haass C. The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBOJ 2008, 27: 336–49.

    Article  CAS  Google Scholar 

  10. Hachiya NS, Kozuka Y, Kaneko K. Mechanical stress and formation of protein aggregates in neurodegenerative disorders. Med Hypotheses 2008, 70: 1034–7.

    Article  PubMed  CAS  Google Scholar 

  11. Wilms H, Zecca L, Rosenstiel P, Sievers J, Deuschl G, Lucius R. Inflammation in Parkinson’s disease and other neurodegenerative diseases: causes and therapeutic implications. Curr Pharm Des 2007, 13: 1925–8.

    Article  PubMed  CAS  Google Scholar 

  12. Iqbal K, Alonso Adel C, et al. Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 2005, 1739: 198–210.

    Article  PubMed  CAS  Google Scholar 

  13. Gasparini L, Terni B, Spillantini MG. Frontotemporal dementia with tau pathology. Neurodegener Dis 2007, 4: 236–53.

    Article  PubMed  Google Scholar 

  14. Takeda A, Hasegawa T, Matsuzaki-Kobayashi M. Mechanism of neural death in synucleinopathy. J Biomed Biotechnol 2006, 2006: 19365.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Williams AJ, Paulson HL. Polyglutamine neurodegenertaion: protein misfolding revisited. Trends Neurosci 2008, 31: 521–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Sakudo A, Ikuta K. Prion protein functions and dysfunction in prion diseases. Curr Med Chem 2009, 16: 380–9.

    Article  PubMed  CAS  Google Scholar 

  17. Sonntag WE, Bennett C, Ingram R, et al. Growth hormon and IGFI modulate local cerebral glucose utilization and ATP levels in model of adult-onset growth hormone deficiency. Am J Physiol Endocrinol Metab 2006, 291: E604–10.

    Article  PubMed  CAS  Google Scholar 

  18. Isgaard J, Aberg D, Nilsson M. Protective and regenerative effects of the GH/IGF-I axis on the brain. Minerva Endocrinol 2007, 32: 103–13.

    PubMed  CAS  Google Scholar 

  19. Dik MG, Pluijm SMF, Jonker C, Deeg DJ, Lomecky MZ, Lips P. Insuline-like growth factor-I (IGF-1) and cognitive decline in older persons. Neurobiol Aging 2003, 24: 573–81.

    Article  PubMed  CAS  Google Scholar 

  20. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reduction in acetylcholine. J Alzheimers Dis 2005, 8: 247–68.

    PubMed  CAS  Google Scholar 

  21. Watanabe T, Miyazaki A, Katagiri T, et al. relationship between serum insulin-like growth factor-1 levels and Alzheimer’s disease and vascular dementia. J Am Geriatr Soc 2005, 53: 1748–53.

    Article  PubMed  Google Scholar 

  22. Gomez JM, Aguilar M, Soler J. Growth hormone and thyrotropin hormone secretion in Alzheimer’ disease. J Nutr Health Aging 2000, 4: 229–32.

    PubMed  CAS  Google Scholar 

  23. Gömez IM, Aguilar M, Navarro MA, Ortolà J, Soler J. GH response to GH-releasing hormone (GHRH) in Alzheimer and vascular dementia. Relation with somatostatin cerebrospinal levels. Ann Endocrinol (Paris) 1996, 57: 107–10.

    Google Scholar 

  24. Pellecchia MT, Pivonello R, Salvatore E, et al. Growth hormone response to arginine test distinguishes multiple system atrophy from Parkinson’s disease and idiopathic late-onset cerebellar ataxia. Clin Endocrinol (Oxf) 2005, 62: 428–33.

    Article  CAS  Google Scholar 

  25. Morselli LL, Bongioanni P, Genovesi M, et al. Growth hormone secretion is impaired in amyotrophic lateral sclerosis. Clin Endocrinol (Oxf) 2006, 65: 385–8.

    Article  CAS  Google Scholar 

  26. Morselli LL, Bongioanni P, Genovesi M et al. Impairment of GH secretion in amyotrophic lateral sclerosis is not affected by riluzole treatment. J Endocrinol Invest 2007, 30: 767–70.

    Article  PubMed  CAS  Google Scholar 

  27. Schneider HJ, Pagotto U, Stalla GK. Central effect of the somatotropic system. Eur J Endocrinol 2003, 149: 377–92.

    Article  PubMed  CAS  Google Scholar 

  28. Skuse D, Lawrence K, Tang J. Measuring social-cognitive functions in children with somatotropic axis dysfunction. Horm Res 2005, 64(Suppl 3): 73–82.

    Article  PubMed  CAS  Google Scholar 

  29. Fernandez S, Fernandez AM, Lopez-Lopez C, Torres-Aleman I. Emerging roles of insulin-like growth factor-I in the adult brain. Growth Horm IGF Res 2007, 17: 89–95.

    Article  PubMed  CAS  Google Scholar 

  30. Vaynman S, Ying Z, Gomez-Pinilla F. Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic plasticity: Neuroscience 2003, 122: 647–57.

    Article  PubMed  CAS  Google Scholar 

  31. Arwert LI, Deijen JB, Drent ML. The relationship between insulinlike growth factor-I levels and cognition in healthy elderly: a metaanalysis. Growth Horm IGF Res 2005, 15: 416–22.

    Article  PubMed  CAS  Google Scholar 

  32. Aleman A, de Vries WR, de Haan EH, Verhaar HJ, Samson MM, Koppeschaar HP. Age-sensitive cognitive function, growth hormon and insulin-like growth factor-1 plasma levels in healthy older men. Neuropsycobiology 2000, 41: 73–8.

    Article  CAS  Google Scholar 

  33. Volpi R, Caffarra P, Scaglioni A et al. Defective 5-HT-receptor-mediated neurotrasmission in the control of growth hormone secretion in Parknson’s disease. Neuropsychobiology 1997, 33: 79–86.

    Article  Google Scholar 

  34. Kiss J, Csaba Z, Csáki A, Halász B. Glutamatergic innervation of growth hormone-releasing containing neurons in the hypothalamic arcuate nucleus nad somatostatin-containin neurons in the anterior periventricular nucleus of the rat. Brain Res Bull 2006, 70: 278–88.

    Article  PubMed  CAS  Google Scholar 

  35. Revill P, Moral MA, Prous JR. Impaired insulin signaling and the pathogenesis of Alzheimer’s disease. Drugs today(Barc) 2006, 42: 785–90.

    Article  CAS  Google Scholar 

  36. Adlerz L, Holback S, Multhaup G, Iverfeldt K. IGF-1-induced processing of the amyloid precursor protein family is mediated by differentsignaling pathways. J Biol Chem 2007, 282: 10203–9.

    Article  PubMed  CAS  Google Scholar 

  37. de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2008, 2: 1101–13.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Reger MA, Watson GS, Frey WH, et al. Effects of intranasal insulin on cognition in memory-impaired old adults:modulation by APOE genotype. Neurobiol Aging 2006, 27: 451–8.

    Article  PubMed  CAS  Google Scholar 

  39. Landreth G. PPRAgamma agonists as new therapeutic agents for the treatment of Alzheimer’s disease. Exp Neurol 2006, 199: 245–8.

    Article  PubMed  CAS  Google Scholar 

  40. Holmberg B, Johansson JO, Poewe W, et al; Growth-Hormone MSA Study Group; European MSA Study Group. Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study. Mov Disord 2007, 22: 1138–44.

    Article  PubMed  Google Scholar 

  41. Torres-Aleman I, Barrios V, Berciano J. The peripheral insulin-like growth factor system in amyotrophic lateral sclerosis and in multiple sclerosis. Neurology 1998, 50: 772–6.

    Article  PubMed  CAS  Google Scholar 

  42. Lai EC, Felice KJ, Festoff BW, et al Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I study group. Neurology 1997, 49, 6: 1621–30.

    Article  PubMed  CAS  Google Scholar 

  43. Mitchell JD, Wokke JHJ, Borasio GD. Recombinanthuman insulinlike growth factor (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2007, 4: CD002064.

    PubMed  Google Scholar 

  44. Smith RA, Melmed S, Sherman B, Frane J, Munsat TL, Festoff BW. Recombinant growth hormone treatement of amyotrophic lateral sclerosis. Muscle Nerve 1993, 16: 624–33.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze per la Salute, Cattedra di Endocrinologia, Università del Molise, contrada Tappino, 86100, Campobasso, Italy

    M. Gasperi (Chair of Endocrinology)

  2. I.R.C.C.S. Neuromed, Pozzilli (IS), Italy

    A. E. Castellano

Authors
  1. M. Gasperi
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  2. A. E. Castellano
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Correspondence to M. Gasperi.

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Gasperi, M., Castellano, A.E. Growth hormone/insulin-like growth factor I axis in neurodegenerative diseases. J Endocrinol Invest 33, 587–591 (2010). https://doi.org/10.1007/BF03346653

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  • DOI: https://doi.org/10.1007/BF03346653

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