The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice

  • Yang, Hyun-Jung (Department of Food and Nutrition, Kookmin University College of Natural Sciences) ;
  • Joo, Yu-Young (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Hong, Bo-Hyun (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Ha, Sung-Ji (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Woo, Ran-Sook (Department of Anatomy and Neuroscience, College of Medicine, Eulji University) ;
  • Lee, Sang-Hyung (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Suh, Yoo-Hun (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Kim, Hye-Sun (Department of Pharmacology, Seoul National University College of Medicine)
  • Received : 2010.07.17
  • Accepted : 2010.08.05
  • Published : 2010.08.30
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Abstract

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

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