Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders.
Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders.
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DOI：
10.1042/bcj20200609
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发表时间：
2021-07-30
期刊：
影响因子：
--
通讯作者：
Pratt MR
中科院分区：
文献类型：
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作者：
Balana AT;Pratt MR
阿尔茨海默氏症和帕金森氏症等神经退行性疾病仍然非常普遍且无法治愈。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。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退行性疾病进展的潜在策略。通过开发和应用能够剖析这种 PTM 机制作用的工具，现在越来越多的证据表明 O-GlcNAc 影响各种重要的神经退行性相关机制，并具有总体保护作用。作为一种附加到众多参与蛋白质质量控制和稳态、代谢、生物能量学、神经元通讯、炎症和程序性死亡的蛋白质上的 PTM，O-GlcNAc 已在神经退行性疾病的动物模型中证明了其有益性，目前多项临床研究正在寻求其上调。
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 upregulation of the endogenous posttranslational modification (PTM) O-GlcNAc has been proposed as a potential strategy to slow down the progression of neurodegeneration. Through 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 upregulation is now being pursued in multiple clinical studies.