Selenium Neurotoxicity and Nutritional Signaling: Integrated Oxidative Stress Pathways in C. elegans

Abstract

Selenium (Se) is a trace element with a narrow margin between beneficial effects and stress from toxic effects. The determinants of the transition from selenium adequacy to toxicity remain unknown. Moreover, the roles of selenoproteins and other adaptive responses also remain unclear. The effects of dynamic and localized redox fluctuations on survival and neurodegeneration also require further investigation. To better understand the underlying mechanisms, several studies utilized the nematode Caenorhabditis elegans (C. elegans) as a model. This review systematically addresses pivotal mechanistic controversies. Thioredoxin reductase-1 (TRXR-1) is the only protein in a small amount of the selenoproteome, and it also has a fully conserved selenocysteine insertion mechanism. Moreover, this systematic review also incorporates the current understanding of the molecular factors that determine selenium homeostasis, ranging from neurotoxicological diseases to biosynthetic circumstances. TRXR-1 supports health benefits such as enhance lipid metabolism, longevity, and stress response. During acute selenium toxicity, TRXR-1 is not needed for survival. Instead, cells defend against adverse effects by using the HIF-1 pathway. Reactive oxygen species (ROS) and hydrogen sulfide (H<inf>2</inf>S) inhibit the prolyl hydroxylase EGL-9 in high-selenium conditions, stabilizing HIF-1 and initiating a transcriptional detoxification process independent of the selenoprotein mechanism. Finally, this review also discuss selective neurotoxicity, a condition in which degeneration that occurs solely in cholinergic ventral cord motor neurons plays a distinctive and precarious role among trace elements.