APPBP1, the Cell Cycle and Alzheimer's Disease

Yuzhi Chen, PhD
McLean Hospital Corporation (Belmont, MA)
Year Awarded:
2002
Grant Duration:
April 1, 2002 to March 31, 2004
Disease:
Alzheimer's Disease
Award Amount:
$100,000
Grant Reference ID:
A2002219
Award Type:
Standard
Award Region:
US Northeastern

APPBP1, the Cell Cycle and Alzheimer's Disease

Details


There is increasing evidence that neurons in Alzheimer's disease (AD) enter the cell cycle (a period of DNA replication leading up to cell division), but because they are locked into a non-dividing state, the attempt to divide causes them to die. Work from many investigators suggests that the amyloid precursor protein (APP) is a signaling molecule whose function may be to regulate cell death. Dr. Chen has found a cell cycle protein called APP-BP1 that binds to APP, and its over-expression in neurons leads to cell death. The present work is based on the hypothesis that AD results from a gradual dysfunction of the APP interaction with APP-BP1, and this dysfunction leads to neuronal death by the abnormal signaling through APP. Dr. Chen will examine the properties of APP and APP-BP1 to identify the protein domains and their function; he will determine where these proteins are located within the cells; he will over-express the proteins in neurons in culture to determine their function; and he will determine if other proteins bind to APP-BP1 and play a role in AD. The data obtained from these studies will help to understand the normal function of APP and AP-BP1 in the brain and identify how these proteins may malfunction in AD resulting in cell death.

Publications

Chen Y, Liu W, Naumovski L, Neve RL. ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to Cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis. J. Neurochem. 2003a, 85:801-809.  

Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL. APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. J. Cell Biol. 2003b; 163(1):27-33.  

Chen Y, Bodles AM, McPhie DL, Neve RL, Mrak RE and W. Griffin WST. APP-BP1 Inhibits Abeta42 Levels by Interacting with Presenilin-1. Molecular Neurodegeneration. 2007, 2:3.  

Chen Y. Z. APP induces neuronal apoptosis through APP-BP1-mediated downregulation of beta-catenin. Apoptosis, 2004, 9:415-22.  

Chen, Y. and Neve, R.L. (2002) APP-BP1 is overexpressed in postmortem Alzheimer's brain hippocampus. Program number 784.17. Abstract Viewer and Itinerary Planner. Washington, DC: Society for Neuroscience, CD-ROM. [conference abstract]
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