Oxidative stress in Down syndrome: unraveling the intertwined pathways for novel target identification

Abstract

Down syndrome (DS) individuals experience chronic and widespread oxidative stress across all organs throughout their lives. While the cause of oxidative stress in DS may be difficult to pinpoint, the myriad perturbations investigated to date share commonalities in terms of their mechanisms. Recent studies highlight five main mechanisms of oxidative stress in DS, namely increased production of reactive oxygen species (ROS), decreased antioxidant defense, impaired mitochondrial biology, defective cellular clearance, and altered metabolism. These mechanisms interact with one another to bring about the overproduction of ROS or a reduction in their clearance. This review attempts to summarize the latest perspective and findings regarding these five mechanisms with emerging evidence within the past five years (2020 to 2025).