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首页 > 医学词汇大全 > Histone deacetylase 6
Histone deacetylase 6

内分泌

关键词内分泌 临床研究术语

词汇介绍

拓展阅读

解析

histone   英 /'hɪstəʊn/   美 /'hɪston/

释    义   n. [生化] 组蛋白

例    句   HISTONE: Histones are crucial in the process of condensing and packing DNA within a cell’s nucleus.组蛋白:组蛋白对于凝结和进一步合成细胞核内的DNA的过程必不可少。

 

deacetylase

释    义   n. 脱乙酰酶

例    句   To reverse the memory loss, doctors inject a compound called a histone deacetylase inhibitor.为了逆转记忆遗失,医生在复合物中添加了组蛋白脱乙酰基酶抑制物。

概述

组蛋白脱乙酰酶6是一类酶,即从ε-N-乙酰赖氨酸氨基酸上删除乙酰基(O=C-CH3)的组蛋白,使组蛋白更紧密地包裹DNA。这很重要,因为DNA包裹在组蛋白周围,并且DNA的表达受乙酰化和脱乙酰化的调节,其作用与组蛋白乙酰转移酶相反。组蛋白脱乙酰酶蛋白现在也称为赖氨酸脱乙酰基酶(KDAC),用以描述其功能而不是其靶标,后者还包括非组蛋白。 功能 组蛋白修饰:组蛋白尾部通常由于其赖氨酸和精氨酸氨基酸上存在胺基而带正电。这些正电荷帮

Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models复制标题

在阿尔茨海默病动物和类器官模型中,乙酰化改变tau相互作用体降解tau

发表时间:2019-11-25

影响因子:7.3

作者: Heesun Choi

期刊:Aging Cell

In AD, post-translational modifications (PTMs) are largely changed. Acetylation is one of the important PTMs that has a variety of biological roles such as histone modulation, metabolism, and stress response. Histone deacetylase 6 (HDAC6), which is unique among histone deacetylases because of its primary cytosolic location, deacetylates several cytosolic proteins, including α-tubulin and tau. HDAC6 is increased in the brains of patients with AD, suggesting that targeting HDAC6 could be a potential therapeutic strategy in AD. Indeed, reducing or inhibiting HDAC6 has been shown to attenuate cognitive deficits, decrease Aβ plaques in AβPPswe/PS1ΔE9 mice, and ameliorate tau pathologies in rTg4510 mice as well as primary cultured neurons. In addition, it is reported that acetylation of tau at several HDAC6-regulated sites competes with phosphorylation of tau and thus inhibits its aggregation. HDAC6 also plays an important role in the ubiquitin–proteasome system (UPS) and autophagy–lysosome system (ALS), both of which are known to be responsible for tau degradation. Because tau is a substrate of HDAC6, HDAC6 might regulate tau degradation. However, the specific mechanism by which HDAC6 inhibition causes tau degradation in AD is not yet known. Moreover, to our knowledge, there has been little or no investigation of the therapeutic effects of HDAC6 inhibition on human brain organoids or AD model animals exhibiting both Aβ and tau pathologies.

译文

在AD中,翻译后修饰(PTMs)发生了很大的变化。乙酰化是一种重要的PTMs,具有组蛋白调节、代谢和应激反应等多种生物学作用。组蛋白脱乙酰基酶6(HDAC6)是组蛋白脱乙酰基酶中唯一的一种,由于其主要的胞浆位置,它可以脱乙酰一些胞浆蛋白,包括α-微管蛋白和tau。AD患者脑内HDAC6含量升高,提示以HDAC6为靶点可能是AD的一种潜在治疗策略。 事实上,减少或抑制HDAC6已被证明能减轻ABPPswe/PS1DE9小鼠的认知缺陷,减少AB斑块,改善rTg4510小鼠和原代培养神经元的tau病理学。此外,据报道,tau在HDAC6调控位点的乙酰化与tau的磷酸化竞争,从而抑制其聚集。 因此,HDAC6在泛素-蛋白酶体系统(UPS)和自噬-溶酶体系统(ALS)中起着重要作用,这两个系统都是tau降解的原因。因为tau是HDAC6的底物,HDAC6可能会调节你的降解。然而,HDAC6抑制导致AD中tau降解的具体机制尚不清楚。此外,据我们所知,关于HDAC6抑制对表现出AB和tau两种病理学的人脑类器官或AD模型动物的治疗作用的研究很少或没有。