Advertisement

Cellular Mechanisms of Brain Damage

  • G. Savettieri
  • I. Di Liegro
  • A. Cestelli

Abstract

In recent years, the great advance in the area of genetics and cellular and molecular neurobiology has led neuroscientists to attempt to discover the cellular and molecular basis of neurological diseases. A neurological disease can be caused by a defective gene, an environmental insult, or by the interaction between environmental factors and preexisting genetic abnormalities. The mechanisms by which cell damage or dysfunction occurs in the nervous system are multiple and related to the nature of the pathological agents. Nevertheless some general mechanisms leading to cell death can be activated independently of the pathological agents. In this review some cellular and molecular mechanisms of brain damage will be focused on, looking at the unifying routes of neuronal cell death.

Keywords

Amyotrophic Lateral Sclerosis Nerve Growth Factor Motor Neuron Disease Brain Damage Familial Amyotrophic Lateral Sclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Choi DW (1996) Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol 6: 667–672PubMedCrossRefGoogle Scholar
  2. 2.
    Greene JG, Greenamyre JT (1996) Bioenergetics and glutamate toxicity. Progr Neurobiol 48: 613–634CrossRefGoogle Scholar
  3. 3.
    Dingledine R, McBain CJ (1999) Glutamate and aspartate. In: Siegel GJ, Agranoff BW, Albers WR et al (ed) Basic neurochemistry. Lippincott-Raven, Philadelphia New York, pp 315–333Google Scholar
  4. 4.
    Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann Rev Neurosci 13: 171–182PubMedCrossRefGoogle Scholar
  5. 5.
    Choi DW (1996) Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol 6: 1261–1276Google Scholar
  6. 6.
    Li H, Yuan J (1999) Deciphering the pathways of life and death. Curr Opin Cell Biol 11: 261–266PubMedCrossRefGoogle Scholar
  7. 7.
    Kowall NW, Ferrante RJ, Martin JB (1987) Patterns of cell loss in Huntington’s disease. Trends Neurosci 10: 24–29CrossRefGoogle Scholar
  8. 8.
    Gusella JF, Wexler NS, Conneally PM et al (1983) A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306: 234–238PubMedCrossRefGoogle Scholar
  9. 9.
    The Huntington Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72: 971–983CrossRefGoogle Scholar
  10. 10.
    Martin JB (1996) Pathogenesis of neurodegenerative disorders: the role of dynamic mutations. Neuroreport 8: 1–7CrossRefGoogle Scholar
  11. 11.
    Duyao MP, Auebarch AB, Ryan A et al (1995) Inactivation of the mouse Huntington’s disease gene homolog Hdh. Science 269: 407–410PubMedCrossRefGoogle Scholar
  12. 12.
    Davis SW, Turmaine M, Cozens BA et al (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation Cell 90: 537–548Google Scholar
  13. 13.
    Gusella JF, McDonald ME (1998) Huntington: a single bait hooks many species. Curr Opin Neurobiol 8: 425–430PubMedCrossRefGoogle Scholar
  14. 14.
    Alves-Rodrigues A, Gregori L, Figueiredo L, Figueiredo-Pereira ME (1998) Ubiquitin, cellular inclusions and their role in neurodegeneration. Trends Neurosci 21: 516–520PubMedCrossRefGoogle Scholar
  15. 15.
    Mulder DW, Kurland LT, Offord KP, Beard CM (1986) Familial adult motor neuron disease: Amyotrophie lateral sclerosis. Neurology 36: 511–517Google Scholar
  16. 16.
    Brown RH Jr (1997) Amyotrophic lateral sclerosis. Insights from genetics. Arch Neurol 54: 1246–1250PubMedCrossRefGoogle Scholar
  17. 17.
    Rosen DR, Siddique T, Patterson D et al (1993) Mutation in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 364: 362PubMedGoogle Scholar
  18. 18.
    Kato T, Katagiri T, Hirano A et al (1989) Lewy body-like hyaline inclusions in sporadic motor neuron disease are ubiquitinated. Acta Neuropathol 77: 391–396PubMedCrossRefGoogle Scholar
  19. 19.
    Rabizadeh S, Gralla EB, Borchelt DR et al (1995) Mutations associated with amyotrophie lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. Proc Natl Acad Sci 92: 3024–3028PubMedCrossRefGoogle Scholar
  20. 20.
    Ghadge G, Lee JP, Bindokas VP et al (1997) Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: molecular mechanisms of neuronal death and protection. J Neurosci 17: 8756–8766PubMedGoogle Scholar
  21. 21.
    Kostic V, Jackson-lewis V, de Bilbao F et al (1997) Bc1–2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 277: 559–562PubMedCrossRefGoogle Scholar
  22. 22.
    Martin JB (1999) Molecular basis of the neurodegenerative disorders. N Engl J Med 340: 1970–1980PubMedCrossRefGoogle Scholar
  23. 23.
    Yuen EC, Howe CL, Yiwen Li et al (1996) Nerve Growth Factor and the neurotrophic factor hypothesis. Brain Dev 18: 362–368PubMedCrossRefGoogle Scholar
  24. 24.
    Gold BG, Mobley WC, Matheson SF (1991) Regulation of axonal caliber, neurofilament content, and nuclear localization in mature sensory neurons by nerve growth factor. J Neurosci 11: 943–955PubMedGoogle Scholar
  25. 25.
    Holtzman DM, Kilbridge J, Li Y et al (1995) TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons. J Neurosci 15: 1567–1576PubMedGoogle Scholar
  26. 26.
    Holtzman DM, Santucci D, Kilbridge J et al (1996) Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci USA 93: 13333–13338PubMedCrossRefGoogle Scholar
  27. 27.
    Diemel LT, Brewster WJ, Fernyhough P, Tomlinson DR (1994) Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. Brain Res Mol Brain Res 21: 171–175PubMedCrossRefGoogle Scholar
  28. 28.
    Apfel SC, Arezzo JC, Brownlee M et al (1994) Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res 634: 7–12PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2000

Authors and Affiliations

  • G. Savettieri
  • I. Di Liegro
  • A. Cestelli

There are no affiliations available

Personalised recommendations