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2007 Grant - Budnik
Genetic Strategies to Elucidate APP Function During Synapse Formation
Vivian Budnik, Ph.D.
University of Massachusetts Medical School
2007 Investigator-Initiated Research Grant
Amyloid precursor protein (APP) is well known for giving rise to beta-amyloid, a tiny yet toxic APP fragment that is believed to disrupt cell-to-cell communication and damage cells in Alzheimer's disease. Despite studying APP for decades, researchers still do not know what its normal function is. Progress has been hampered by the existence in mammals of several similar proteins, or homologues, which may compensate when APP activity is perturbed experimentally.
In fruit flies, however, there is one APP-like gene (APPL). Vivian Budnik, Ph.D., and colleagues plan to take advantage of this to study the normal function of APP. They have found that APPL is present in synapses — the tiny junctions through which neurons communicate with each other — where it may help regulate cell-to-cell signaling. They also found that the APPL level in synapses is altered by mutation of another protein called "Arrow." Interestingly, Arrow mutations have very similar effects in fruit flies to overproduction of APP, which can cause Alzheimer-like pathology.
The researchers plan to investigate the relationships among APP, Arrow and synaptic activity in more detail. Arrow may be a key player in a cell-signaling pathway that regulates the development of synapses. This suggests that APP may also play an important role in neurodevelopment. This research may yield new insights into the biological role of APP in the healthy and Alzheimer brain.