DnaJs被丰富在tau调节器中
Abigail R Esquivel1, Shannon E Hill1, Laura J Blair2
1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.
International journal of biological macromolecules
|October 18, 2023
概括
分子伴侣,特别是来自DnaJ家族的DnaJB6b,可以显著减少有毒的tau蛋白积累和播种,为神经退行性疾病提供潜在的治疗点.
科学领域:
- 神经生物学 神经生物学 神经生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 异常的蛋白积累和播种是神经退行性疾病的关键病理特征.
- 分子陪伴者可以影响病理,但它们的作用通常被单独研究.
研究的目的:
- 通过高通量测试来识别调节播种的分子伴侣.
- 调查已识别的陪伴者对病理学的特定影响.
主要方法:
- 使用Tau RD P301S细胞进行半高吞吐量FRET生物传感器测定.
- 通过活细胞成像,大约50个陪伴者被选,以检测它们对种植的影响.
- 对关键陪伴者进行过度表达和淘汰 (shRNA) 研究.
主要成果:
- 五个陪伴者显著影响了tau种植,其中三个来自DnaJ家族的陪伴者表现出了显著的影响.
- 过度表达DnaJA2,DnaJB1和DnaJB6b降低了tau水平;DnaJB1和DnaJB6b的淘汰显示出与tau水平的逆相关性.
- DnaJB6b 特别降低了总水平,部分是通过增强的蛋白质体降解,并与复合体相互作用.
结论:
- 分子伴侣的DnaJ家族,特别是DnaJB6b,在调节病理方面表现出强大的活性.
- DnaJB6b降低水平并与复合体相互作用的能力表明它在病变中的治疗潜力.
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