与X结合的泛特异性酶11增加了女性病的脆弱性
Yan Yan1, Xinming Wang2, Dale Chaput3
1Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA; Department of Molecular Medicine, USF Health College of Medicine, Tampa, FL, USA.
Cell
|October 5, 2022
概括
女性
科学领域:
- 神经科学
- 遗传学
- 生物化学
背景情况:
- 女性患阿尔茨海默病 (AD) 的风险更高,而的负担也比男性高.
- 这种性差异在阿尔茨海默病的脆弱性上的生物学基础尚不清楚.
研究的目的:
- 调查X结合的泛素特异性酶11 (USP11) 在性别特异性阿尔茨海默病 (AD) 发病过程中的作用.
- 探索USP11作为女性阿尔茨海默病的潜在治疗点.
主要方法:
- 在体外和体内模型,人类AD脑组织分析.
- 研究了USP11在二化,乙化和聚合中的作用.
- 在病小鼠模型中利用USP11的遗传消除.
主要成果:
- USP11通过在lysine-281中启动tau二化来增加病态tau的聚合.
- USP11逃脱X无活化,导致女性的水平更高.
- 消除USP11保护的雌性小鼠的tau病理和认知衰退.
结论:
- 通过USP11介导的双化有助于女性易患阿尔茨海默病 (AD).
- 抑制USP11是一种潜在的治疗策略,可以保护女性免受阿尔茨海默氏症和其他病.
相关概念视频
X-linked Traits
55.2K
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
55.2K
Sex-linked Disorders
102.7K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.7K
The Proteasome
1.1K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.1K


