神经元内核包容性疾病的病理变化与在高位压力下异常的FUS相互作用有关
Hui Wang1, Yilei Zheng1, Jiaxi Yu1
1Department of Neurology, Peking University First Hospital, Beijing 100034, China.
Neurobiology of disease
|December 25, 2023
概括
压力通过与FUS相互作用,诱导有毒多糖氨酸 (N2CpolyG) 在神经元内核包容性疾病 (NIID) 中的聚合,破坏细胞应激反应并导致微RNA失调. 这揭示了NIID.的潜在治疗点.
科学领域:
- 神经遗传学 神经遗传学
- 分子病原体的产生.
- 细胞应激反应的应激反应
背景情况:
- 神经内核包容性疾病 (NIID) 是由NOTCH2NLC中CGG重复扩张引起的.
- 翻译过的多糖氨酸 (N2CpolyG) 蛋白质形成有毒的核内含物 (IIs),但形成因子和致病性尚不清楚.
研究的目的:
- 研究环境压力对N2CpolyG IIs形成的影响.
- 阐明NIID病原体背后的分子机制.
主要方法:
- 利用SH-SY5Y细胞模型来研究在高位压力下N2CpolyG的行为.
- 使用同局部化研究检查了蛋白质与蛋白质相互作用.
- 在细胞模型和患者组织中分析了microRNA表达.
主要成果:
- 超的压力诱导了N2CpolyG转移到细胞核和细胞中的IIs形成.
- 在IIs中与FUS共同局部化N2CpolyG,破坏了细胞质应激颗粒的形成.
- 在NIID模型和患者中,微RNA的表达失调.
结论:
- 压力是N2CpolyG诱导的内核包容形成和NIID中神经元损伤的关键因素.
- 与N2CpolyG的FUS相互作用在NIID的发病过程中起着至关重要的作用.
- 恢复FUS水平可能通过使microRNA表达正常化为NIID提供治疗策略.
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