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

Amyloid-beta (Aß)-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 Aß peptide, plays a significant role in effecting cellular pathogenesis. Here we apply a particularly effective form of exogenous Aß, 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 Aß-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