Andre Son
Research Mentor: Tuo Ji
Mentor Department: Neurology, Medicine
Author(s): Andre Son, Tuo Ji, Kevin Charland, Catherine Kaczorowski
Session: Session 6 (3:00 PM – 3:50 PM)
Presentation Type: Poster 38
Abstract
Oxidative stress (OxS) is highly implicated in aging and many neurodegenerative diseases including Alzheimer’s disease (AD). We QTL (Quantitative Trait Loci) mapped GSR (Glutathione Reductase) as a genetic modifier of cognitive resilience to AD in our genetically diverse AD-BXD mouse panel. Heritable variants in GSR modified its protein abundance, which was associated with differential cognitive performance in AD-BXD mice. We cross referenced GSR in human data in an extensively phenotyped AD cohort (ROSMAP) and found it to be similarly implicated in human AD cognitive performance. Our nomination of GSR–an integral component of a cell-ubiquitous antioxidant cycle–in cognitive outcomes has been recently supported by novel work that similarly enhanced Glutathione (GSH) abundance and improved cognitive performance through supplementation of GSH precursors (GlyNAC; Glycine + N-acetylcysteine). Since both GSR and GlyNAC supplementation increases the abundance of GSH, we plan to evaluate whether GlyNAC supplementation increases GSR abundance thereby improving not only the GSH reserve but also the recycling capacity. Using primary fibroblasts isolated from mice that segregate the GSR locus we mapped, we will assess the effect of GlyNAC supplementation in attenuating OxS and increasing GSR protein abundance. Establishing a link between GlyNAC supplementation and GSR levels can help translate the robustly protective effects of GlyNAC in normal cognitive aging to the context of AD related cognitive decline.
