Role of APP in synaptogenesis
In mouse models with either no APP expression or with expression of only the mutant form of APP and neurons derived from both sets of mice, we found that APP may serve as bridging molecules for the formation of the synapse. When the synapse isn't properly formed, due to the lack of proper APP function, then the synapse activity is low or absent. Our results will allow us to understand how this may be happening, what happens when APP is mutated or when beta-amyloid plaques are present, and what we can do to counteract this effect to enhance the synaptic activity and neural communication. The results of this study will be the basis for future discoveries of new therapies for increasing the synaptic activity found in AD, with the goal to improve cognitive function.
Yang, L., Wang, Z., Wang, B., Justice, N., and Zheng, H. (2009) Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J. Neurosci., 29: 15660-15668.
Li, H., Wang, B., Wang, Z., Guo, Q., Tabuchi, K., Hammer, R., Sudhof, T., and Zheng, H. (2010). Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP. Proc. Natl. Acad. Sci. USA, 107: 17362-17367.
Wiese, M., Antebi, A. and Zheng, H. (2010). Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans. PLoS ONE, 5: e12790.
First published on: June 10, 2008
Last modified on: August 20, 2010