Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice.
10.4196/kjpp.2010.14.4.229
- Author:
Hyun Jung YANG
1
;
Yuyoung JOO
;
Bo Hyun HONG
;
Sung Ji HA
;
Ran Sook WOO
;
Sang Hyung LEE
;
Yoo Hun SUH
;
Hye Sun KIM
Author Information
1. Department of Food and Nutrition, Kookmin University College of Natural Sciences, Seoul 136-702, Korea.
- Publication Type:Original Article
- Keywords:
Amyloid precursor protein binding protein-1;
Amyloid precursor protein;
Alzheimer's disease;
cell cycle;
Tg2576 mice
- MeSH:
Alzheimer Disease;
Amyloid;
Animals;
Apoptosis;
Brain;
Cell Cycle;
Cricetinae;
DNA;
Hippocampus;
Mice;
Models, Animal;
Neural Stem Cells;
Neurons;
Protein Binding;
RNA, Small Interfering
- From:The Korean Journal of Physiology and Pharmacology
2010;14(4):229-233
- CountryRepublic of Korea
- Language:English
-
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.
