Skip to main content
SpringerLink
Log in

Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down Syndrome and Alzheimer’s disease brain is downregulated at the mRNA and dysregulated at the protein level

  • Conference paper
The Molecular Biology of Down Syndrome

Summary

Deteriorated migration, axonal pathfinding and wiring of the brain is a main neuropathological feature of Down Syndrome (DS). Information on the underlying mechanisms is still limited, although basic functions of a series of growth factors, cell adhesion molecules, guidance factors and chemoattractants for brain histogenesis have been reported.

We used proteomics to detect differences in protein expression between control, DS and Alzheimer’s disease brains: In five individual brain regions of 9 individuals of each group we performed two dimensional electrophoresis with MALDI — identification of proteins and determined mRNA levels of DRP-2.

Significantly decreased mRNA levels of DRP-2 in four brain regions of patients with DS but not with AD as compared to controls were detected. 2D electrophoresis revealed variable expression of DRP-2 proteins, which showed a high heterogeneity per se. Dysregulation of DRP-2 was found in brains of patients with DS and AD presenting with an inconsistent pattern, which in turn may reflect the inconsistent neuropathological findings in patients with DS and AD.

The decrease of mRNA DRP-2 steady state levels in DS along with deteriorated protein expression of this repulsive guidance molecule of the semaphorin/collapsin family, may help to explain deranged migration and histogenesis of DS brain and wiring of AD brain.

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

Access this chapter

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Becker LE, Armstrong DL, Chan F (1986) Dendritic atrophy in children with Down’s syndrome. Ann Neurol 20: 520–532

    Article  PubMed  CAS  Google Scholar 

  • Becker L, Mito T, Takashima S, Onodera K (1991) Growth and development of the brain in Down Syndrome. In: Epstein CJ (ed) The morphogenesis of Down Syndrome. Wiley-Liss, New York, p 133

    Google Scholar 

  • Bernert G, Nemethova M, Cairns N, Lubec G (1996) Decreased cyclin dependent kinase in brain of patients with Down Syndrome. Neurosci Lett 216: 68–70

    Article  PubMed  CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254

    Article  PubMed  CAS  Google Scholar 

  • Byk T, Ozon S, Sobel A (1998) The ulip family phosphoproteins — common and specific properties. Eur J Biochem 254: 14–24

    Article  PubMed  CAS  Google Scholar 

  • Crome L, Cowie V, Slater E (1966) A statistical note of cerebellar and brain stem weight in mongolism. J Ment Defic Res 10: 69–77

    Google Scholar 

  • Drescher U, Kremoser C, Handwerker C, Loeschinger J, Noda M, Bonhoeffer F (1995) In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph — receptor tyrosine kinases. Cell 82: 359–370

    Article  PubMed  CAS  Google Scholar 

  • Epstein CJ (1995) Down Syndrome (Trisomy 21). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease. McGraw Hill, New York, pp 749–794

    Google Scholar 

  • Fountoulakis M, Langen H (1997) Identification of proteins by matrix-assisted laser desorption ionization-mass spectroscopy following in-gel digestion in low — salt, nonvolatile buffer and simplified peptide recovery. Anal Biochem 250: 153–156

    Article  PubMed  CAS  Google Scholar 

  • Gaetano C, Matsuo T, Thiele CJ (1997) Identification and characterisation of a retinoic acid regulated human homologue of the unc-33-like phosphoprotein gene (hUlip) from neuroblastoma cells. J Biol Chem 272: 12195–12201

    Article  PubMed  CAS  Google Scholar 

  • Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM (1995) Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376: 509–514

    Article  PubMed  CAS  Google Scholar 

  • Goshima Y, Kawakami T, Hori H, Sugiyama Y, Takasawa S, Hashimoto Y, Kagoshima-Maezono M, Takenaka T, Misu Y, Strittmatter SM (1997) A novel action of collapsin: collapsin-1 increases antero-and retrograde axoplasmic transport independently of growth cone collapse. J Neurobiol 33: 316–328

    Article  PubMed  CAS  Google Scholar 

  • Grenningloh G, Rehm EJ, Goodman CS (1991) Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule. Cell 67: 45–57

    Article  PubMed  CAS  Google Scholar 

  • Hamajima N, Matsuda K, Sakata S, Tamaki N, Sasaki M, Nonaka M (1996) A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene 180: 157–163

    Article  PubMed  CAS  Google Scholar 

  • Jokusch H, Nave K-A, Grenningloh G, Schmitt-John T (1997) Molecular genetics of nervous and neruromuscular systems. In: Davies RW, Morris BJ (eds) Molecular biology of the neuron. BIOS Scientifique Publishers, Oxford, pp 21–66

    Google Scholar 

  • Kolodkin AL, Matthes DJ, Goodman CS (1993) The semaphorin genes encode a family of transmembranre and secreted growth cone guidance molecules. Cell 75:1389–1399

    Article  PubMed  CAS  Google Scholar 

  • Kuwada J (1995) Development of the zebrafish nervous system: genetic analysis and manipulation. Curr Opin Neurobiol 5: 50–54

    Article  PubMed  CAS  Google Scholar 

  • Langen H, Roeder D, Juranville J-F, Fountoulakis M (1997) Effect of the protein application mode and the acrylamide concentration on the resolution of protein spots separated by two-dimensional gel electrophoresis. Electrophoresis 18: 2085–2090

    Article  PubMed  CAS  Google Scholar 

  • Li W, Herman RK, Shaw JE (1992) Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33. Genetics 132: 675–689

    PubMed  CAS  Google Scholar 

  • Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75: 217–227

    Article  PubMed  CAS  Google Scholar 

  • McMaster GK, Carmichael GG (1977) Analysis by single and double stranded nucleic acids on polytacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci (USA) 74: 4835–4841

    Article  CAS  Google Scholar 

  • Marin-Padilla M (1976) Pyramidal cell abnormalities in the motor cortex of a child with Down’s Syndrome. J Comp Neurol 167: 63–75

    Article  PubMed  CAS  Google Scholar 

  • Minturn JE, Fryer HJ, Geschwind DH, Hockfield S (1995) TOAD-64, a gene expressed early in neuronal differentiation in the rat, is related to unc-33, a C.elegans gene involved in axon outgrowth. J Neurosci 15: 6757–6766

    PubMed  CAS  Google Scholar 

  • Mirra SS, Heyman A, McKeel D, Sumi S, Crain B J (1991) The consortium to establish a registry for Alzheimer disease (CERAD). II. Standardisation of the neuro-pathological assessment of Alzheimer’s disease. Neurology 41: 479–486

    Article  PubMed  CAS  Google Scholar 

  • Rehder H (1981) Pathology of trisomy 21. In: Burgio GR, Fraccaro M, Tiepolo L, Wolf U (eds) Trisomy 21. An International Symposium. Springer, Berlin Heidelberg New York Tokyo, p 57

    Chapter  Google Scholar 

  • Schmidt-Sidor B, Wisniewski KE, Shepard TH, Sersen A (1990) Brain growth in Down Syndrome subjects 15–22 weeks of gestational age and birth to 60 months. Clin Neuropathol 9: 181–195

    PubMed  CAS  Google Scholar 

  • Seeger M, Tear G, Ferres-Marco D, Goodman CS (1993) Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance towards or away from the midline. Neuron 10: 409–426

    Article  PubMed  CAS  Google Scholar 

  • Seidl R, Greber S, Schuller E, Bernert G, Cairns N, Lubec G (1997) Evidence against increased oxidative DNA-damage in Down Syndrome. Neurosci Lett 235: 137–140

    Article  PubMed  CAS  Google Scholar 

  • Stahl B, Mueller B, von Boxberg Y, Cox EC, Bonhoeffer F (1990) Biochemical characterization of a putative axonal guidance molecule of the chick visual system. Neuron 5: 733–743

    Article  Google Scholar 

  • Sylvester PE (1986) The anterior commissure in Down’s syndrome. J Ment Defic Res 30: 19–25

    PubMed  Google Scholar 

  • Takashima S, Ieshima A, Nakamura H, Becker LE (1989) Dendrites, dementia and the Down Syndrome. Brain Dev 2: 131–143

    Article  Google Scholar 

  • Tierney MC, Fisher RH, Lewis AJ, Torzitto ML, Snow WG, Reid DW, Nieuwstraaten P, Van Rooijen LAA, Derks HJGM, Van Wijk R, Bischop A (1988) The NINCDA-ADRDA work group criteria for the clinical diagnosis of probable Alzheimer’s disease. Neurology 38: 359–364

    Article  PubMed  CAS  Google Scholar 

  • Van Vactor D, Sink H, Fambrough D, Tsoo R, Goodman CS (1993) Genes that control neuromuscular specificity in Drosophila. Cell 73: 1137–1153

    Article  PubMed  CAS  Google Scholar 

  • Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differently expressed in the nervous system. J Neurosci 16: 6197–6207

    PubMed  CAS  Google Scholar 

  • White BA, Bancroft FC (1982) Cytoplasmic dot hybridization. Simple analysis of mRNA levels in multiple small cell or tissue samples. J Biol Chem 257: 8569–8575

    PubMed  CAS  Google Scholar 

  • Wisniewski KE, Bobinski M (1991) Hypothalamic abnormalities in Down syndrome. In: Epstein CJ (ed) The morphogenesis of Down Syndrome. Wiley — Liss, New York, p 153

    Google Scholar 

  • Wisniewski KE, Laure-Kamionowska M, Connell F, Wen GY (1986) Neuronal density and synaptogenesis in the postnatal stage of brain maturation in Down syndrome. In: Epstein CJ (ed) The neurobiology of Down Syndrome. Raven, New York, p 29

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    Prof. Dr. G. Lubec, K. Krapfenbauer & M. Gratzer

  2. Department of Biochemistry, Nagoya City University, Nagoya, Japan

    M. Nonaka

  3. Brain Bank, Institute of Psychiatry, University of London, UK

    N. Cairns

  4. F. Hoffmann — La Roche, Basel, Switzerland

    M. Fountoulakis

Authors
  1. Prof. Dr. G. Lubec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Krapfenbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Gratzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Cairns
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Fountoulakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Universitäts-Kinderklinik, Wien, Österreich

    G. Lubec

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Wien

About this paper

Cite this paper

Lubec, G., Nonaka, M., Krapfenbauer, K., Gratzer, M., Cairns, N., Fountoulakis, M. (1999). Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down Syndrome and Alzheimer’s disease brain is downregulated at the mRNA and dysregulated at the protein level. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6380-1_10

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83377-3

  • Online ISBN: 978-3-7091-6380-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation