2010 Grants - Xu

Appoptosin, an APP Binding Proapoptotic Protein, Mediates Neuronal Death

Huaxi Xu, Ph.D.
Burnham Institute for Medical Research
La Jolla, California

2010 Investigator-Initiated Research Grant

Amyloid precursor protein (APP) is a well-characterized protein in the brain that is cut into pieces, one of which is beta-amyloid. Beta-amyloid is toxic to nerve cells and forms amyloid plaques, one of the characteristic features of Alzheimer pathology. Because APP plays such an important role in the development of Alzheimer pathology, its production, transport and activity are of great interest.

Huaxi Xu, Ph.D., and colleagues have discovered a protein that binds to APP and which appears to trigger programmed cell death. The researchers plan to characterize the function of this protein, which they have named appoptosin. They plan to create antibodies to appoptosin, which can then be used to visualize the localization of the protein and measure its levels at different times. Dr. Xu's team will study the signaling pathways by which appoptosin triggers cell death, and how that process is influenced by binding of APP. Finally, the researchers will study how APP and appoptosin are involved in the development of Alzheimer pathology, and whether appoptosin levels change in the brains of mice with Alzheimer-like pathology. These studies will characterize an important new protein potentially involved in the development of Alzheimer pathology.