Serum- and glucocorticoid-induced kinase 1, a new therapeutic target for autophagy modulation in chronic diseases

• Published in: Expert opinion on therapeutic targets Vol. 24; no. 3; p. 231
• Main Authors: Maestro, Inés, Boya, Patricia, Martinez, Ana
• Format: Journal Article
• Language: English
• Published: England 03.03.2020
• Subjects: Allosteric Regulation - drug effects; Animals; Autophagy - drug effects; Chronic Disease - drug therapy; Drug Development; Drug Discovery; Humans; Immediate-Early Proteins - metabolism; Molecular Targeted Therapy; Protein-Serine-Threonine Kinases - metabolism; neurodegenerative diseases; therapeutic target; autophagy; kinase inhibitors; SGK1
• ISSN: 1744-7631
• DOI: 10.1080/14728222.2020.1730328

: Autophagy, a basic cellular degradation pathway essential for survival, is altered both in aging and in many chronic human diseases, including infections, cancer, heart disease, and neurodegeneration. Identifying new therapeutic targets for the control and modulation of autophagy events is therefore of utmost importance in drug discovery. Serum and glucocorticoid activated kinase 1 (SGK1), known for decades for its role in ion channel modulation, is now known to act as a switch for autophagy homeostasis, and has emerged as a novel and important therapeutic target likely to attract considerable research attention in the coming years. : In this general review of SGK1 we describe the kinase's structure and its roles in physiological and pathological contexts. We also discuss small-molecule modulators of SGK1 activity. These modulators are of particular interest to medicinal chemists and pharmacists seeking to develop more potent and selective drug candidates for SGK1, which, despite its key role in autophagy, remains relatively understudied. : The main future challenges in this area are (i) deciphering the role of SGK1 in selective autophagy processes (e.g. mitophagy, lipophagy, and aggrephagy); (ii) identifying selective allosteric modulators of SGK1 with specific biological functions; and (iii) conducting first-in-man clinical studies.