Abstract: Impairment of TrkB Receptor Endocytosis by Beta-Amyloid Oligomers is Rescued by UCH-L1 (2011 SACNAS National Conference)

Saturday, October 29, 2011

Hall 1-2 (San Jose Convention Center)

Brittany Aguilar, BS , Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA

Carl Cotman, PhD , Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA

Wayne Poon, PhD , Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA

When the neurotrophin BDNF binds to its receptor TrkB at the axon terminal, the signal is propagated via retrograde transport. Previous research has shown that in Alzheimer’s disease (AD) early impairments may result from neurotrophic signaling deficits due to the presence of soluble ß-amyloid (Aß). It has been suggested that a possible mechanism for Aß is the sequestering of ubiquitin, thus making it a limiting factor in receptor cellular sorting. Using the previously described microfluidic culture chambers, we were able to show this retrograde transport deficit and then recover the effect through the use of UCH-L1, a ubiquitin hydroxylase that removes ubiquitin from proteins that are targeted for degradation. The results that we obtained using the immunocytochemistry promote limiting ubiquitin as a possible mechanism through which Aß affects the cell.