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Changes in signal transduction in Alzheimer’s disease

  • S. Shimohama
  • H. Ninomiya
  • T. Saitoh
  • R. D. Terry
  • R. Fukunaga
  • T. Taniguchi
  • M. Fujiwara
  • J. Kimura
  • M. Kameyama
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 30)

Summary

We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer’s disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, l-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (βII) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (βII)-immunopositive neurons. Anti-PKC (α) faintly stained entire plaques and surrounding glial cells. Anti-PKC (βI) stained dystrophic plaque neurites. Anti-PKC (βII) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.

Keywords

NMDA Receptor Neuritic Plaque Excitatory Amino Acid Receptor Phosphorylate Amyloid Precursor Protein Entire Plaque 
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 1990

Authors and Affiliations

  • S. Shimohama
    • 1
    • 6
  • H. Ninomiya
    • 1
  • T. Saitoh
    • 2
  • R. D. Terry
    • 2
  • R. Fukunaga
    • 3
  • T. Taniguchi
    • 3
  • M. Fujiwara
    • 4
  • J. Kimura
    • 1
  • M. Kameyama
    • 5
  1. 1.Department of Neurology, Faculty of MedicineKyoto UniversityJapan
  2. 2.Department of Neurosciences, School of MedicineUniversity of CaliforniaSan DiegoUSA
  3. 3.Department of NeurobiologyKyoto Pharmaceutical UniversityJapan
  4. 4.Department of Pharmacology, Faculty of MedicineKyoto UniversityJapan
  5. 5.Department of NeurologySumitomo HospitalJapan
  6. 6.Department of Neurology, Faculty of MedicineKyoto UniversitySakyo-ku, Kyoto 606Japan

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