Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(22), P. 12918 - 13019

Published: Nov. 7, 2024

O-Linked β-N-acetylglucosamine (O-GlcNAc) is an essential, dynamic monosaccharide post-translational modification (PTM) found on serine and threonine residues of thousands nucleocytoplasmic proteins. The installation removal O-GlcNAc controlled by a single pair enzymes, transferase (OGT) O-GlcNAcase (OGA), respectively. Since its discovery four decades ago, has been diverse classes proteins, playing important functional roles in many cellular processes. Dysregulation homeostasis implicated the pathogenesis disease, including neurodegeneration, X-linked intellectual disability (XLID), cancer, diabetes, immunological disorders. These foundational studies disease biology have motivated efforts to target therapeutically, with multiple clinical candidates under evaluation. In this review, we describe characterization biochemistry OGT OGA, regulation, development OGA inhibitors, pathophysiology, progress modulators, emerging opportunities for targeting O-GlcNAc. This comprehensive resource should motivate further study into function inspire strategies therapeutic modulation

Language: Английский