通过准自-溶酶体机械和蛋白质病变来利用产前的甜味缓解
Zheping Huang1, Shibin Cheng1, Sukanta Jash1
1Department of Pediatrics, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, 02905, USA.
Experimental & molecular medicine
|May 17, 2024
概括
孕前 (PE) 涉及到自和胎盘中的蛋白质积累受损. 三糖和乳三糖的治疗方法通过恢复自和减少有毒蛋白质聚合物,对PE有希望.
科学领域:
- 产科和妇科 产科和妇科
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 孕前 (PE) 是一种严重的妊娠并发症,病因不明,导致显著的孕产妇和胎儿发病率.
- 与阿尔茨海默氏症相似的自和蛋白质病变受损已经在PE的胎盘中被确定.
- 对于PE的有效治疗策略受到其不太了解的潜在机制的阻碍.
研究的目的:
- 调查受损自和蛋白质病变在孕前病原发生中的作用.
- 通过准这些途径,评估三和乳三作为孕前的潜在治疗剂.
- 阐明这些脱糖化合物在PE中发挥作用的分子机制.
主要方法:
- 利用暴露于缺氧的初级人类热囊细胞来建模与PE相关的胎盘功能障碍.
- 给人体热囊细胞和PE的人性化小鼠模型注射了三和乳三.
- 评估了使用各种技术的自恢复,蛋白质聚合物抑制和超结构变化.
- 分析了TFEB的核转移,并对胎盘组织进行了RNA-seq.
主要成果:
- 三糖和乳三糖恢复了自,并抑制了人类细胞中的有毒蛋白质聚合.
- 这些脱糖化合物通过正常化胎盘自和减少蛋白质聚合,在小鼠模型中防止了PE类特征.
- 治疗增加了TFEB核转位,增强了自-溶酶生物发生.
- RNA-seq分析显示PE相关转录组在对三糖和乳三糖的反应中正常化.
结论:
- 损伤的自和蛋白质病变代表了先兆子的新型分子基础.
- 三糖和乳三糖通过向这些病理途径,证明了对孕前的治疗潜力.
- 这些分糖为治疗这种严重的妊娠并发症提供了一个有希望的新途径.
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