Functional Interaction of APP-CTF with G-alphaS in Brain

Project Summary

Dr. Angèle Parent and her team's research efforts focus on understanding the molecular and cellular mechanisms associated with the development of Alzheimer's disease (AD). They are using cell culture and mouse models in their research to clarify the role of a genetically engineered protein that may affect the progression of AD. Interestingly, their study identified a novel interaction of a portion of the amyloid precursor protein (APP) that resides inside the cell, termed the “intracellular domain,” with a signaling protein termed the “G-alphaS.” This molecular interaction may impact brain functions such as learning and memory. Indeed, their recent findings demonstrated that membrane accumulation of amyloid precursor protein's intracellular domain results in inhibition of one of the important signaling cascades associated with AD pathology. Accordingly, in order to prevent or delay AD, these experiments investigate the therapeutic potential of developing a version of the amyloid precursor protein intracellular domain that remains tethered to the cell membrane.

To accomplish this they are using a virus to deliver the modified protein to mice brains. Consequences on brain functions are investigated by examining changes in neuron development and their chemistry. The viral brain administration strategy is the first step toward a comprehensive evaluation of the beneficial effect associated with brain expression of this modified protein. The ultimate goal is to develop novel therapeutic strategies applicable to humans to fight this devastating disorder. Parent and her team are greatly encouraged by their preliminary findings and confident that these investigations will yield significant advances.