(96d) Aβ Activation of a Tyrosine Kinase, Fyn, through a Cell Surface Integrin Interaction: Implications for Alzheimer's | AIChE

(96d) Aβ Activation of a Tyrosine Kinase, Fyn, through a Cell Surface Integrin Interaction: Implications for Alzheimer's

Authors 

Ramos, I. - Presenter, University of Maryland Baltimore County
Good, T. - Presenter, University of Maryland Baltimore County


Beta-amyloid peptide (Aβ) is the main protein constituent found in senile plaques in Alzheimer's disease (AD). Aggregated Aβ plays a role in neurodegeneration associated with AD however, the relationship between Aβ structure and the mechanism by which Aβ interacts with cells is still poorly understood. In this work we used FRET and confocal microscopy to examine the distances between Aβ bound to the cell surface and various cell surface receptors and found that Aβ bound to within 5 nm of cell surface integrins. We measured Aβ induced tyrosine kinase activity, and found that Aβ activated fyn, a tyrosine kinase linked to cell response to oxidative stress, but also hypothesized to modulate activity of ion channels associated with long term potentiation, learning and memory. Finally, we performed a series of experiments using FRET, confocal microscopy, and flow cytometry to demonstrate the connection between Aβ-integrin interaction and fyn activation. This work helps illustrate early steps in Aβ cell signaling that may be associated with cellular changes that can be directly related to loss of memory in Alzheimer's disease.