α-Ketoglutarate Dehydrogenase in Alzheimer’s Disease

  • John P. Blass
  • Kwan-Fu Rex Sheu
  • Rudolph E. Tanzi
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

Since ancient times, a creative tension has existed between two viewpoints on illness. One, associated with the Platonic physicians of the island of Cnos, looks on diseases as specific entities which can be classified like plants. From this viewpoint, the specific patient in the examining room is a more or less close copy of an idealized patient. In modern times, this view was developed with particular strength by Sydenham in London in the 1600s. The second viewpoint, associated with the Hippocratic physicians of the island of Cos, views illness as occurring when an organism can no longer remain in balance with the challenges of its environment. In modern times, this view was put forward with particular clarity by Claude Bernard in Paris in the 1800s. He emphasized that an illness occurs when living organisms cannot maintain their “milieu interne” in the face of the challenges of their environment.

Keywords

Oxidative Metabolism Amyloid Precursor Protein ApoE Gene Culture Skin Fibroblast Selective Vulnerability 
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. Adolfsson, R. Gottfries C.G., Oreland, L., et al., Increased activity of brain and platelet monoamine oxidase in dementia of the Alzheimer type, Life Sci. 27:1029.Google Scholar
  2. Ali, G., Wasco, W., Cai, X. et al, 1994, Isolation, characterization, and mapping of the dihyrodlipoyl succinyltransferase [E2k] of human α-ketoglutarate dehyrogenase complex, Somat. Cell Mol Genet. 20:99.PubMedCrossRefGoogle Scholar
  3. Beal, M.F., 1992, Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative diseases? Ann. Neural. 31:119.CrossRefGoogle Scholar
  4. Bick, K., Amaducci, L., and Pepeu, G., 1987, The early story of Alzheimer’s disease. Livinia Press, Padua.Google Scholar
  5. Blass, J.P., 1993a, Pathophysiology of the Alzheimer’s syndrome, Neurology 43 (suppl 4):S25.Google Scholar
  6. Blass, J.P., 1993b, The cultured fibroblast model, J. Neural. Trans. (Suppl) 44:87.Google Scholar
  7. Blass, J.P., Baker, A.C., Ko, L. et al, 1991, Expression of Alzheimer antigens in cultured skin fibroblasts, Arch. Neurol. 48:709.PubMedCrossRefGoogle Scholar
  8. Blass, J.P., and Gibson, G.E., 1991, The role of oxidative abnormalities in the pathophysiology of Alzheimer’s Disease, Rev. Neurol. (Paris) 147:513.Google Scholar
  9. Blass, J.P., and Gibson, G.E., 1993, Nonneural markers in Alzheimer disease, Alz. Dis. Assoc. Dis. 6:205.CrossRefGoogle Scholar
  10. Blass, P., Hoyer, S., and Nitsch, R., 1992, In reply, Arch. Neurol. 49:800.CrossRefGoogle Scholar
  11. Blass, J.P., Milne, J.A., and Rodnight, R., 1977, Newer concepts of psychiatric diagnosis and biochemical research on mental illness. Lancet 1:738.PubMedCrossRefGoogle Scholar
  12. Blass, J.P., and Poirier, J., 1995, Pathophysiology of the Alzheimer’s Syndrome, In press.Google Scholar
  13. Blass, J.P., Sheu, K.-F.R., and Cederbaum, J.M., 1988, Energy metabolism in disorders of the nervous system, Rev. Neurol. (Paris) 144:543.Google Scholar
  14. Butterworth, R.F., and Besnard, A.M., 1990, Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer’s disease, Metab. Brain Dis. 4:179.CrossRefGoogle Scholar
  15. Cai, X., Sabo, P., Ali, G. et al, 1994, A pseudogene of dihyrdrolipoyl succinyltransferase (E2k) found by PCR amplification and direct sequencing in rodent-human cell hybrid DNAs. Somat. Cell Mol. Genet. 20:339.PubMedCrossRefGoogle Scholar
  16. Cheng, B., and Mattson, M.P., 1992, Glucose deprivation elicits neurofibrillary tangle-likeantigenic changes in hippocampal neurons: Prevention by NGF and bFGF, Exp. Neurol. 117:114.PubMedCrossRefGoogle Scholar
  17. Endoh, M., Pulsinelli, W.A., and Wagner, J.A., 1994, Transient global ischemia induces dynamic changes in the expression of bFGF and the FGF receptor, Brain Res. 22:76.CrossRefGoogle Scholar
  18. Fillit, H., Ding, W.H., Buee, L. et al, 1991, Elevated circulating tumor necrosis factor levels in Alzheimer’s disease. Neurosci Lett 129:318.PubMedCrossRefGoogle Scholar
  19. Gabuzda, D., Busciglio, J., Chen, L.B. et al, 1994, Inhibition of eneergy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative, J. Biol. Chem. 269:13628.Google Scholar
  20. Garrod, A.E., 1923, Inborn Errors of Metabolism, Oxford, London.Google Scholar
  21. Gibson, G.E., and Blass, J.P., 1982, Metabolism and neurotransmission, in: Handbook of Neurochemistry, A. Lajtha, ed., vol. 3, 2nd ed., Plenum Press, N.Y.Google Scholar
  22. Gibson, G.E., Blass, J.P., Huang, H.-M. et al, 1991, The cellular basis of delerium and its relevance to age-related disorders including Alzheimer’s disease, Int. Psychogeriatrics 3:373.CrossRefGoogle Scholar
  23. Gibson, G.E., Pulsinelli, W.A., and Blass, J.P., 1981, Brain dysfunction in mild to moderate hypoxia, Am. J. Med. 70:1247.PubMedCrossRefGoogle Scholar
  24. Gibson, G.E., Sheu, K.-F.R., Blass, J.P. et al, 1988, Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer’s Disease, Arch. Neurol. 45:836.PubMedCrossRefGoogle Scholar
  25. Henneberry, R.A., 1989, The role of energy in the toxicity of excitatory amino acids, Neurobiol. Aging 10:611.PubMedCrossRefGoogle Scholar
  26. Hirsch, J.A., and Gibson, G.E., 1984, Selective alterations of neurotransmitter release by low oxygen in vitro, Neurochem. Res. 9:1039.PubMedCrossRefGoogle Scholar
  27. Huang, H.-M., and Gibson, G.E., 1993, Altered β-receptor stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors, J. Biol. Chem. 268:14616.PubMedGoogle Scholar
  28. Ko, L., Sheu, K.-F.R., and Blass, J.P., 1993, Chemical neuroanatomy of energy metabolism: immunohistochemical studies in relation to selective vulnerability, J. Neurochem. 61: S70.Google Scholar
  29. Makar, T.K., Cooper, A.J.L., Tofel-Grehl, B., et al, 1995, Carnitine, carnitine acetyltransferase, and glutathione in Alzheimer brain, Neurochem. Res. 20:705.PubMedCrossRefGoogle Scholar
  30. Mattson, M.P., Cheng, B., Culwell, A.R. et al, 1993, Evidence for excitoprotective and intraneuronal calcium regulating for secreted forms of the β-amyloid precursor protein. Neuron 10:246.CrossRefGoogle Scholar
  31. Mattson, M.P., and Goodman, Y., 1995, Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. Brain Res. 676:219–224.PubMedCrossRefGoogle Scholar
  32. McGeer, P.L., McGeer, E., Kawamata, T. et al, 1991, Reactions of the immune system in chronic degenerative neurological diseases, Can. J. Neurol. Sci. 18 (suppl 3): 376.PubMedGoogle Scholar
  33. Nakano, K., Takase, C., Sakamoto, T. et al, 1994, Isolation, characterization, and structural organization of the gene and pseudogene for the dihyrolipoylamide succinyltransferase component of the 2-oxoglutarate dehydrogenase complex, Eur. J. Biochem. 224:179.PubMedCrossRefGoogle Scholar
  34. Paoletti, F., and Mocali, A., 1991, Enhanced proteolytic activities in cultured fibroblasts of Alzheimer patients are revealed by peculiar transketolase alterations, J. Neurol. Sci. 105:211.PubMedCrossRefGoogle Scholar
  35. Parker, W.D., Filley, C.M., and Parks, J.K., 1990, Cytochrome oxidase deficiency in Alzheimer’s disease, Neurology 40: 1302.Google Scholar
  36. Rogers, J., Cooper, N.R., Webster, S. et al, 1992, Complement activation by β-amyloid in Alzheimer’s disease, Proc. Nad. Acad. Sci. (USA) 89:10016.CrossRefGoogle Scholar
  37. Roses, A.D., 1995, Alzheimer’s disease as a model of molecular gerontology, J. NIH Res. 7:51.Google Scholar
  38. Sheu, K.-F.R., Clarke, D.D., Kim, Y.T. et al, 1988, Studies of the transketolase abnormality in Alzheimer’s disease, Arch. Neurol. 45:841.PubMedCrossRefGoogle Scholar
  39. Sheu, K.-F.R., Cooper, A.J.L., Lindsay, J.G., et al, 1994, Abnormality of the β-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer’s Disease, Ann. Neurol. 35:312.PubMedCrossRefGoogle Scholar
  40. Sims, N.R., Finegan, J.M., and Blass, J.P., 1987, Altered metabolic properties of cultured skin fibroblasts in Alzheimer’s disease, Ann. Neurol. 21:451.PubMedCrossRefGoogle Scholar
  41. Van Zuylen, A.J., Bosman, G.J.C.G.M., Ruitenbeek, W., et al, 1992, No evidence for reduced thrombocyte cytochrome oxidase activity in Alzheimer’s Disease, Neurology 42:1246.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • John P. Blass
    • 1
  • Kwan-Fu Rex Sheu
    • 1
  • Rudolph E. Tanzi
    • 2
  1. 1.Altschul Laboratory for Dementia Research and Will Rogers Institute, Burke Medical Research InstituteCornell University Medical CollegeWhite PlainsUSA
  2. 2.Neurogenetics Laboratory and Laboratory of Genetics and AgingMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations