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Reduced aldehyde dehydrogenase levels in the brain of patients with Down Syndrome

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The Molecular Biology of Down Syndrome

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Summary

Aldehyde dehydrogenase (ALDH) is a key enzyme in fructose, acetaldehyde and oxalate metabolism and represents a major detoxification system for reactive carbonyls and aldehydes. In the brain, ALDH exerts a major function in the metabolism of biogenic aldehydes, norepinephrine, dopamine and diamines and γ-aminobutyric acid. Subtractive hybridization studies in Down Syndrome (DS) fetal brain showed that mRNA for ALDH are downregulated. Here we studied the protein levels in the brain of adult patients. The proteins from five brain regions of 9 aged patients with DS and 9 controls were analyzed by two-dimensional (2-D) gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry. ALDH levels were reduced in the brain regions of at least half of the patients with Down Syndrome, as compared to controls. The decreased ALDH levels in the DS brain may result in accumulation of aldehydes which can lead to the formation of plaques and tangles reflecting abnormally cross-linked, insoluble and modified proteins, found in aged DS brain. Furthermore, we constructed a 2-Dmap including approximately 120 identified human brain proteins.

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Authors and Affiliations

  1. Department of Pediatrics, University of Vienna, Austria

    G. Lubec & O. Labudova

  2. Institute of Psychiatry, Brain Bank, London, UK

    N. Cairns

  3. F. Hoffmann — La Roche, Ltd., PRPG-T, Building 93-444, CH-4070, Basel, Switzerland

    P. Berndt, H. Langen & M. Fountoulakis

Authors
  1. G. Lubec
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  2. O. Labudova
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  3. N. Cairns
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  4. P. Berndt
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  5. H. Langen
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  6. M. Fountoulakis
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Editor information

Editors and Affiliations

  1. Universitäts-Kinderklinik, Wien, Österreich

    G. Lubec

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© 1999 Springer-Verlag Wien

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Lubec, G., Labudova, O., Cairns, N., Berndt, P., Langen, H., Fountoulakis, M. (1999). Reduced aldehyde dehydrogenase levels in the brain of patients with Down Syndrome. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_2

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  • DOI: https://doi.org/10.1007/978-3-7091-6380-1_2

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83377-3

  • Online ISBN: 978-3-7091-6380-1

  • eBook Packages: Springer Book Archive

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