Analysis of gene expression changes in amyloid-beta (ADDL) and CAT-SKL antioxidant treated primary rat neuronal cells

Amyloid-beta (Aβ)-induced neurotoxicity is a major contributor to the pathologies associated with Alzheimer’s disease (AD). The formation of reactive oxygen species (ROS), and early response induced by the Aβ peptide, plays a significant role in effecting cellular pathogenesis. Here we apply a particularly effective form of exogenous Aβ, i.e., amyloid beta-derived diffusible ligands (ADDLs), to cultured primary cortical/hippocampal neurons to elicit ROS and drive cellular dysfunction. To prevent and even reverse such effects, we employed a cell-penetrating, peroxisome-targeted, protein biologic - called CAT-SKL. We show the recombinant enzyme enters neurons, reverses Aβ-induced oxidative stress, and increases cell viability. Dramatic restorative effects on damaged neuronal processes were also observed. CAT-SKL, a targeted antioxidant, may represent a new therapeutic approach for treatment disorders, like Alzheimer’s disease, where oxidative stress is manifest. Preclinical testing is warranted and ongoing Primary Rat E18 coritical/hippocampal neurons (derived from Sprague Dawley E18 cortical/hippocampus tissue obtained from BrainBits®, Springfield, IL) were treated with ADDLs in the presence or absence of the targeted antioxidant CAT-SKL to investigate genes that displayed altered expression in response to treatmetns total RNA was isolated and analyzed in an Agilent two-color experiment. Two biological replicates of each condition were directly compared, ratios are treated relative to control (untreated)