内分泌
词汇介绍
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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
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。这些正电荷帮助组蛋白尾巴与DNA骨架上带负电荷的磷酸基团相互作用并结合。乙酰化通常发生在细胞中，通过将胺变成酰胺来中和组蛋白的正电荷，并降低组蛋白与DNA结合的能力。这种减少的结合允许染色质扩增，允许基因转录发生。组蛋白脱乙酰基酶去除那些乙酰基，增加组蛋白尾巴的正电荷，并促进组蛋白和DNA骨架之间的高亲和力结合。DNA结合增加会凝结DNA结构，从而阻止转录。
非组蛋白效果：仅在通过修饰组蛋白和染色质结构来调节基因转录的背景下考虑组蛋白脱乙酰酶是一个错误，尽管这似乎是主要功能。蛋白质的功能，活性和稳定性可以通过翻译后修饰来控制。蛋白质的磷酸化可能是最广泛研究和理解变形例，其中某些氨基酸残基被具有磷酸化作用的蛋白激酶或通过去磷酸化作用的磷酸酶磷酸化。赖氨酸残基的乙酰化正以类似的机制出现，其中非组蛋白被乙酰化酶和脱乙酰基酶作用。正是在这种情况下，发现HDAC与多种非组蛋白蛋白相互作用-其中一些是转录因子和共调节因子，有些则不是。
临床相关性
该基因的突变与阿尔茨海默氏病有关。该蛋白的过度表达与肿瘤发生和细胞存活有关。HDAC6还促进癌细胞的转移。
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
影响指数：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.
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