Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse.
Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse.
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DOI：
10.3390/biom13091324
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发表时间：
2023-08-29
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
表观遗传化合物已经成为有吸引力的小分子，用于靶向阿尔茨海默病（AD）的多方面。虽然AD不成比例地影响女性，但目前大多数研究表观遗传化合物治疗AD的文献都没有报告性别特异性结果。这是值得注意的，因为越来越多的证据表明，表观遗传化合物本质上影响男性和女性不同。该手稿探讨了在3xTg-AD小鼠模型中长期、低剂量给予临床相关组蛋白脱乙酰酶抑制剂西达米特（Tucidinostat）后观察到的性二态性。我们发现，西达米特治疗显着改善葡萄糖耐量和增加表达的葡萄糖转运蛋白在大脑中的男性。我们还报告了西达明治疗的小鼠中总tau蛋白的减少。在西达明处理的小鼠中，雄性小鼠的差异表达基因比雌性小鼠大得多。神经炎症通路和淀粉样蛋白加工通路中涉及的基因在西达明处理的雄性中大多上调，而在西达明处理的雌性中下调。这项工作强调了药物发现项目需要考虑性别作为一个生物变量，以促进翻译。
Epigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer’s disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results. This is remarkable because there is rising evidence that epigenetic compounds intrinsically affect males and females differently. This manuscript explores the sexual dimorphism observed after chronic, low-dose administration of a clinically relevant histone deacetylase inhibitor, chidamide (Tucidinostat), in the 3xTg-AD mouse model. We found that chidamide treatment significantly improves glucose tolerance and increases expression of glucose transporters in the brain of males. We also report a decrease in total tau in chidamide-treated mice. Differentially expressed genes in chidamide-treated mice were much greater in males than females. Genes involved in the neuroinflammatory pathway and amyloid processing pathway were mostly upregulated in chidamide-treated males while downregulated in chidamide-treated females. This work highlights the need for drug discovery projects to consider sex as a biological variable to facilitate translation.
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影响因子：
3.7
作者：
Hanson JE;La H;Plise E;Chen YH;Ding X;Hanania T;Sabath EV;Alexandrov V;Brunner D;Leahy E;Steiner P;Liu L;Scearce-Levie K;Zhou Q
通讯作者：
Zhou Q
DOI：
10.3233/jad-122308
发表时间：
2013
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Claxton A;Baker LD;Wilkinson CW;Trittschuh EH;Chapman D;Watson GS;Cholerton B;Plymate SR;Arbuckle M;Craft S
通讯作者：
Craft S
影响因子：
5.8
作者：
Kennard, Matilda R.;Nandi, Manasi;Chapple, Sarah;King, Aileen J.
通讯作者：
King, Aileen J.
影响因子：
7.9
作者：
Lu T;Mar JC
通讯作者：
Mar JC
DOI：
10.1007/s00210-018-1589-y
发表时间：
2019-01
期刊：
Naunyn-Schmiedeberg's archives of pharmacology
影响因子：
--
作者：
Gawel K;Gibula E;Marszalek-Grabska M;Filarowska J;Kotlinska JH
通讯作者：
Kotlinska JH