Selenot, also known as Selenoprotein T (SELENOT), is a thioredoxin-like enzyme anchored at the endoplasmic reticulum (ER) membrane. It plays a crucial role in multiple biological processes. SELENOT is involved in ER proteostasis, endocrine homeostasis, and neuroprotection. It also contributes to insulin and corticotropin biosynthesis and release by regulating ER proteostasis [4]. Genetic models, such as gene knockout mouse models, are valuable for studying its functions.

In mouse models, brain-specific SELENOT knockout led to a significant decrease in the number of tyrosine hydroxylase-positive neurons in certain brain areas like the area postrema, A11 cell group, zona incerta in females, and the hypothalamus in both females and males, indicating its importance in the establishment of the catecholaminergic neuronal system [1]. In a facial nerve injury model in female rats, a mimetic peptide PSELT derived from SELENOT promoted nerve regeneration by increasing axonal myelination [2]. In heart failure models, PSELT attenuated systemic inflammation, myocardial injury, and improved contractile impairment [3].

In conclusion, SELENOT is essential for maintaining ER homeostasis, which in turn impacts endocrine functions and neural development. Gene knockout mouse models have revealed its role in neurodegenerative and cardiovascular disease-related processes, providing insights into potential therapeutic strategies targeting SELENOT-related pathways in these disease areas.

References:

1. Godefroy, David, Boukhzar, Loubna, Mallouki, Ben Yamine, Tillet, Yves, Anouar, Youssef. 2022. SELENOT Deficiency in the Mouse Brain Impacts Catecholaminergic Neuron Density: An Immunohistochemical, in situ Hybridization and 3D Light-Sheet Imaging Study. In Neuroendocrinology, 113, 193-207. doi:10.1159/000522091. https://pubmed.ncbi.nlm.nih.gov/35066506/

2. Pothion, Hugo, Lihrmann, Isabelle, Duclos, Celia, Marie, Jean-Paul, Anouar, Youssef. 2022. The SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats. In Journal of neuroscience research, 100, 1721-1731. doi:10.1002/jnr.25098. https://pubmed.ncbi.nlm.nih.gov/35730417/

3. De Bartolo, Anna, Pasqua, Teresa, Romeo, Naomi, Angelone, Tommaso, Rocca, Carmine. 2024. The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure. In Journal of translational medicine, 22, 375. doi:10.1186/s12967-024-05192-w. https://pubmed.ncbi.nlm.nih.gov/38643121/

4. Anouar, Youssef, Lihrmann, Isabelle, Falluel-Morel, Anthony, Boukhzar, Loubna. 2018. Selenoprotein T is a key player in ER proteostasis, endocrine homeostasis and neuroprotection. In Free radical biology & medicine, 127, 145-152. doi:10.1016/j.freeradbiomed.2018.05.076. https://pubmed.ncbi.nlm.nih.gov/29800653/