Abstract

Healthy cells continually produce low levels of reactive oxygen species (ROS), which are buffered by multiple antioxidant systems. Imbalance between ROS production and elimination results in oxidative stress, which has been implicated in aging and in numerous human diseases, including cancer and diabetes. Selenoproteins are a family of proteins that contain the amino acid selenocysteine, encoded by an in-frame UGA. Those selenoproteins whose function is identified are catalytically active in redox processes, representing one of the main enzymatic antioxidant systems and important mediators of the beneficial role of selenium in human health. Nevertheless, the function of most selenoproteins remains unknown; this included Selenoprotein N (SelN), the only selenoprotein directly associated with a human genetic disease. Mutations of the SelN gene cause SEPN1-related myopathy, a particular early-onset muscle disorder. Recent studies have identified SelN as a key protein in cell protection against oxidative stress and redox-related calcium homeostasis. Furthermore, an effective ex vivo treatment of SelN deficiency has been identified, paving the way to a clinical therapy. In this review we discuss the physiological and pathophysiological role of SelN and the interest of SEPN1-related myopathy as a model paradigm to understand and target therapeutically other selenoproteins involved in human health and disease.