Alzheimer’s disease (AD) is the most common cause of dementia and the number of elderly patients suffering from AD has been steadily increasing. Despite worldwide efforts to cope with this disease, little progress has been achieved with regard to identification of effective therapeutics. Thus, active research focusing on identification of new therapeutic targets of AD is ongoing. Among the new targets, post-translational modifications which modify the properties of mature proteins have gained attention. O-GlcNAcylation, a type of PTM that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) to a protein, is being sought as a new target to treat AD pathologies. O-GlcNAcylation has been known to modify the two important components of AD pathological hallmarks, amyloid precursor protein, and tau protein. In addition, elevating O-GlcNAcylation levels in AD animal models has been shown to be effective in alleviating AD-associated pathology. Although studies investigating the precise mechanism of reversal of AD pathologies by targeting O-GlcNAcylation are not yet complete, it is clearly important to examine O-GlcNAcylation regulation as a target of AD therapeutics. This review highlights the mechanisms of O-GlcNAcylation and its role as a potential therapeutic target under physiological and pathological AD conditions.

中文翻译：

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O-GlcNAcylation作为阿尔茨海默氏病的治疗靶点。

阿尔茨海默氏病（AD）是痴呆症的最常见原因，患有AD的老年患者人数一直在稳步增加。尽管全世界为应对这种疾病作出了努力，但是在鉴定有效治疗剂方面进展甚微。因此，正在进行集中于鉴定AD的新治疗靶标的积极研究。在新的靶标中，修饰成熟蛋白特性的翻译后修饰已引起关注。O-GlcNAcylation，一种与O相连的β- N相连的PTM类型-乙酰氨基葡萄糖（O-GlcNAc）的蛋白质，正在寻求作为治疗AD病理的新目标。已知O-GlcNAcylation修饰AD病理学标志的两个重要成分，淀粉样蛋白前体蛋白和tau蛋白。另外，提高AD动物模型中的O-GlcNAcylation水平已显示出可有效减轻AD相关的病理。尽管研究针对O-GlcNAcylation靶向逆转AD病理的确切机制的研究尚未完成，但将O-GlcNAcylation调节作为AD治疗的靶标显然很重要。这篇综述强调了O-GlcNAcylation的机制及其在生理和病理AD条件下作为潜在治疗靶标的作用。