Korean J Physiol Pharmacol.  2010 Aug;14(4):229-233. 10.4196/kjpp.2010.14.4.229.

Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice

• Yang HJ
• Joo Y
• Hong BH
• Ha SJ
• Woo RS
• Lee SH
• Suh YH
• Kim HS

• KMID: 2285407
• DOI: http://doi.org/10.4196/kjpp.2010.14.4.229

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.

Keyword

Amyloid precursor protein binding protein-1; Amyloid precursor protein; Alzheimer's disease; cell cycle; Tg2576 mice

MeSH Terms

Alzheimer Disease
Amyloid
Animals
Apoptosis
Brain
Cell Cycle
Cricetinae
DNA
Hippocampus
Mice
Models, Animal
Neural Stem Cells
Neurons
Protein Binding
RNA, Small Interfering
Amyloid
DNA
RNA, Small Interfering