Huynh Duc Tan, Boyce Michael
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Isr J Chem. 2023 Feb;63(1-2). doi: 10.1002/ijch.202200071. Epub 2022 Nov 15.
O-linked β--acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification in mammals, decorating thousands of intracellular proteins. O-GlcNAc cycling is an essential regulator of myriad aspects of cell physiology and is dysregulated in numerous human diseases. Notably, O-GlcNAcylation is abundant in the brain and numerous studies have linked aberrant O-GlcNAc signaling to various neurological conditions. However, the complexity of the nervous system and the dynamic nature of protein O-GlcNAcylation have presented challenges for studying of neuronal O-GlcNAcylation. In this context, chemical approaches have been a particularly valuable complement to conventional cellular, biochemical, and genetic methods to understand O-GlcNAc signaling and to develop future therapeutics. Here we review selected recent examples of how chemical tools have empowered efforts to understand and rationally manipulate O-GlcNAcylation in mammalian neurobiology.
O-连接的β-N-乙酰葡糖胺（O-GlcNAc）是哺乳动物中一种普遍存在的翻译后修饰，修饰数千种细胞内蛋白质。O-GlcNAc循环是细胞生理学诸多方面的重要调节因子，在许多人类疾病中失调。值得注意的是，O-GlcNAcylation在大脑中含量丰富，许多研究已将异常的O-GlcNAc信号与各种神经系统疾病联系起来。然而，神经系统的复杂性和蛋白质O-GlcNAcylation的动态性质给神经元O-GlcNAcylation的研究带来了挑战。在这种情况下，化学方法对于理解O-GlcNAc信号和开发未来治疗方法的传统细胞、生化和遗传方法而言，是一种特别有价值的补充。在这里，我们回顾了一些最近的例子，说明化学工具如何助力在哺乳动物神经生物学中理解和合理操纵O-GlcNAcylation的努力。
