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Roles of Aβ and carboxyl terminal peptide fragments of amyloid precursor protein in Alzheimer disease

  • Y.-H. Suh
  • H.-S. Kim
  • J. P. Lee
  • C. H. Park
  • S.-J. Jeong
  • S.-S. Kim
  • J.-C. Rah
  • J.-H. Seo
  • S.-S. Kim
Conference paper

Summary

Several lines of evidence indicate that Aβ may play an important role in the pathogenesis of AD. However, there are several discrepancies between the production of Aβ and the development of the disease.

Thus, Aβ may not be the sole active fragment of β-amyloid precursor protein (βAPP) in the neurotoxicity assiciated with AD.

We focused on the amyloidegenic carboxyl terminal fragments of βAPP containing the full length of Aβ (CT105). We synthesized a recombinant carboxyl-terminal 105 amino acid fragment of βAPP and examined the effects of CT105 and Aβ on cultured neurons, Ca++ uptake into rat brain microsomes, Na+ -Ca++ exchange activity, ion channel forming activity in lipid bilayers and passive avoidance performance of mice.

Our results suggest that the cytotoxic and channel inducing effects of CT105 are much more potent than that of Aβ and toxic mechanisms of CT105 are different from those of Aβ.

Taken together, these lines of evidence postulate that CT is an alternative toxic element important in the generation of the symptoms common to AD.

Keywords

SHSY5Y Cell Xenopus Oocyte Planar Lipid Bilayer Amyloid Precursor Protein Mutation Aurin Tricarboxylic Acid 
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.

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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • Y.-H. Suh
    • 1
    • 4
  • H.-S. Kim
    • 1
    • 4
  • J. P. Lee
    • 1
    • 4
  • C. H. Park
    • 1
    • 4
  • S.-J. Jeong
    • 1
    • 4
  • S.-S. Kim
    • 2
  • J.-C. Rah
    • 1
    • 4
  • J.-H. Seo
    • 1
    • 4
  • S.-S. Kim
    • 3
  1. 1.Department of PharmacologyCollege of Medicine, Seoul National UniversityChongno-gu, SeoulKorea
  2. 2.Department of PharmacologyCollege of Medicine, Kang Won National UniversitySeoulKorea
  3. 3.Department of AnatomyCollege of Medicine, Chung Ang UniversitySeoulKorea
  4. 4.Biomedical Brain Research Center, NIHSeoulKorea

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