School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Korea.
Department of Health Science and Technology, Sungkyunkwan University, Seoul, 06351, Korea.
Neuromolecular Med. 2020 Jun;22(2):171-193. doi: 10.1007/s12017-019-08584-0. Epub 2020 Jan 1.
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.
阿尔茨海默病（AD）是痴呆症最常见的病因，患 AD 的老年患者人数一直在稳步增加。尽管全世界都在努力应对这种疾病，但在确定有效的治疗方法方面几乎没有取得进展。因此，正在进行专注于确定 AD 新治疗靶点的积极研究。在新的靶点中，修饰成熟蛋白质特性的翻译后修饰引起了关注。O-连接的 β-N-乙酰葡萄糖胺（O-GlcNAc）修饰蛋白质的 O-GlcNAcylation 作为治疗 AD 病理的新靶点正在被研究。O-GlcNAcylation 已被证实可以修饰 AD 病理特征的两个重要组成部分，即淀粉样前体蛋白和 tau 蛋白。此外，在 AD 动物模型中升高 O-GlcNAcylation 水平已被证明可有效缓解 AD 相关的病理。虽然研究靶向 O-GlcNAcylation 逆转 AD 病理的确切机制的研究尚未完成，但显然需要检查 O-GlcNAcylation 调节作为 AD 治疗的靶点。本综述强调了 O-GlcNAcylation 的机制及其在生理和病理 AD 条件下作为潜在治疗靶点的作用。
