Louisiana Tech University, Department of Biomedical Engineering
Newly discovered neural receptor's role in Aβ1-42 pathogenesis of Alzheimer's disease
Annadora Bruce-Keller, Ph.D., Pennington Biomedical University
Yuri Voziyanov, Ph.D., Louisiana Tech University, Department of Biology
Pilot Project (May 1, 2012 – April 30, 2013)
A recently discovered neurotransmitter receptor, the α7β2 nicotinic acetylcholine receptor (α7β2-nAChR) is expressed in neurons in the septum and hippocampus of the brain. These regions experience a loss of cholinergic neurons in Alzheimer's disease (AD) which adversely affects cognition and memory. This new receptor is similar in functional attributes to the well-recognized α7-nAChR. Notably, α7-nAChR-mediated endocytosis of amyloid-β1-42 (Aβ1-42) peptide results in intracellular deposits of Aβ1-42. Intracellular deposits have been identified as an early step in AD etiopathology. However, the effects of α7β2-nAChR-mediated endocytosis by this newly discovered receptor have not been studied. We will separately express α7β2-nAChR and α7-nAChR in the neuroepithelial SH-EP1 cell line to compare Aβ1-42 internalization and key intracellular effects. Receptor subunits will be differentially labeled with fluorescent proteins incorporated into the intracellular domain to facilitate documentation of their positions via 3D confocal microscopy. Aβ1-42 will be stained for quantification and colocalization analyses. Cells will be incubated with oligomeric Aβ1-42 and the amount and location(s) of the internalized peptide will be quantified as will its colocalization with the intracellular targets in our study.