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糖刺激可预防记忆损伤。

Sugar Kick Prevents Memory Impairment.

出版信息

J Med Chem. 2019 Nov 27;62(22):10059-10061. doi: 10.1021/acs.jmedchem.9b01668. Epub 2019 Oct 31.

Abstract

Pathological hyperphosphorylation of tau and subsequent aggregation to form neurofibrillary tangles (NFTs) is closely related to progression of neurodegenerative diseases such as Alzheimer's disease (AD) and progressive supranuclear palsy. A recent study showed that MK-8719 () is a selective and potent small molecule inhibitor of human -GlcNAcase (hOGA). The pharmacological inhibition of OGA, the sole enzyme involved in removal of a sugar moiety (-GlcNAc residue) from tau, increases global -GlcNAc levels within the brain and reduces tau phosphorylation. The OGA inhibitor slows neurodegeneration and improves cognitive function in AD and related tauopathies. Here, we discuss the findings of that study and the development of OGA inhibitors as novel therapeutic strategy for treatment of age-related memory impairment in neurodegenerative diseases.

摘要

tau 的病理性过度磷酸化以及随后聚集形成神经原纤维缠结(NFTs)与神经退行性疾病的进展密切相关,如阿尔茨海默病(AD)和进行性核上性麻痹。最近的一项研究表明,MK-8719()是人类 -GlcNAcase(hOGA)的选择性和强效小分子抑制剂。OGA 的药理学抑制作用是唯一一种从 tau 上去除糖基部分(-GlcNAc 残基)的酶,可增加大脑内的全局 -GlcNAc 水平并降低 tau 的磷酸化。OGA 抑制剂可减缓 AD 和相关 tau 病中的神经退行性变并改善认知功能。在这里,我们讨论了该研究的结果以及 OGA 抑制剂作为治疗神经退行性疾病相关年龄相关性记忆障碍的新型治疗策略的发展。

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