Neurodegenerative diseases such as Alzheimer's and Parkinson's remain highly prevalent and incurable disorders. A major challenge in fully understanding and combating the progression of these diseases is the complexity of the network of processes that lead to progressive neuronal dysfunction and death. An ideal therapeutic avenue is conceivably one that could address many if not all of these multiple misregulated mechanisms. Over the years, chemical intervention for the up-regulation of the endogenous posttranslational modification (PTM) O-GlcNAc has been proposed as a potential strategy to slow down the progression of neurodegeneration. Through the development and application of tools that allow dissection of the mechanistic roles of this PTM, there is now a growing body of evidence that O-GlcNAc influences a variety of important neurodegeneration-pertinent mechanisms, with an overall protective effect. As a PTM that is appended onto numerous proteins that participate in protein quality control and homeostasis, metabolism, bioenergetics, neuronal communication, inflammation, and programmed death, O-GlcNAc has demonstrated beneficence in animal models of neurodegenerative diseases, and its up-regulation is now being pursued in multiple clinical studies.

中文翻译：

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O-GlcNAcylation 在神经退行性疾病中改变的机制作用

阿尔茨海默氏症和帕金森氏症等神经退行性疾病仍然是非常普遍且无法治愈的疾病。充分理解和对抗这些疾病进展的一个主要挑战是导致进行性神经元功能障碍和死亡的过程网络的复杂性。可以想象，一种理想的治疗途径可以解决许多（如果不是全部）这些多重失调机制中的许多问题。多年来，上调内源性翻译后修饰 (PTM) O-GlcNAc 的化学干预已被提议作为减缓神经变性进展的潜在策略。通过开发和应用允许剖析此 PTM 的机械作用的工具，现在有越来越多的证据表明 O-GlcNAc 影响各种重要的神经变性相关机制，具有整体保护作用。作为附加在参与蛋白质质量控​​制和体内平衡、代谢、生物能量学、神经元通讯、炎症和程序性死亡的众多蛋白质上的 PTM，O-GlcNAc 已在神经退行性疾病的动物模型中显示出有益效果，其上调是现在正在进行多项临床研究。