Amyloid-beta neuroprotection mediated by a targeted antioxidant.

ABSTRACT: Amyloid-beta (A?)-induced neurotoxicity is a major contributor to the pathologies associated with Alzheimer's disease (AD). The formation of reactive oxygen species (ROS), an early response induced by the peptide and oligomeric derivatives of A?, plays a significant role in effecting cellular pathogenesis. Here we employ particularly toxic forms of A? with cultured primary cortical/hippocampal neurons to elicit ROS and drive cellular dysfunction. To prevent and even reverse such effects, we utilized a cell-penetrating, peroxisome-targeted, protein biologic--called CAT-SKL. We show the recombinant enzyme enters neurons, reverses A?-induced oxidative stress, and increases cell viability. Dramatic restorative effects on damaged neuronal processes were also observed. In addition, we used DNA microarrays to determine A?'s effects on gene expression in neurons, as well as the ability of CAT-SKL to modify such A?-induced expression profiles. Our results suggest that CAT-SKL, a targeted antioxidant, may represent a new therapeutic approach for treatment of disorders, like Alzheimer's disease, that are driven through oxidative stress. Preclinical testing is ongoing.

SUBMITTER: Giordano CR 

PROVIDER: S-EPMC4021325 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature