神经退行性疾病相关长链非编码RNA的高灵敏检测及功能调控基础研究

神经退行性疾病严重威胁人们的生活质量及身心健康，研究发现神经退行性疾病的发病与长链非编码RNA有密切关系。然而目前对长链非编码RNA进行实际分析时所面临的逆转录扩增过程繁琐、检测灵敏度低以及难以实现原位功能调控分析的难题制约了其在神经退行性疾病早期预警及信号通路研究方面的进一步应用。本项目拟利用核酸分子探针作为识别工具，发展新的传感机理及信号放大手段，在外周血、细胞与活体三个层面实现神经退行性疾病相关长链非编码RNA-BACE1-AS的高灵敏检测与高分辨成像，拓展核酸分子探针在神经退行性疾病早期预警方面的应用前景；同时基于功能化DNA三链分子开关构建智能核酸纳米探针传感体系调控BACE1-AS在神经退行性疾病进程中的生理功能，深入了解BACE1-AS与神经退行性疾病发病机制的关系，为神经退行性疾病的病因治疗提供新的思路和手段。

Neurodegenerative diseases seriously affect people's quality of life and physical and mental health. Studies have demonstrated that neurodegenerative diseases and long non-coding RNA (lncRNA) are closely related to the incidence. However, due to the cumbersome RT-PCR process, low sensitivity and inability to regulate its function efficiently in situ, it remains a challenge to achieve early waring and understand the specific mechanism of lncRNA in neurodegenerative diseases. Herein, we seek support of this project for high sensitive BACE1-AS detection in peripheral blood and high-resolution imaging in vivo by using new nucleic acid probe sensing platforms and developing new sensing mechanism and functional regulation strategy. We chose BACE1-AS which is related to neurodegenerative disease as the specific research object while the early diagnosis and etiological treatment of neurodegenerative diseases is taken as the overall goal. In addition, intelligent nucleic acid nanoprobe sensing platform will also be proposed based on DNA triple-helix molecular switch to realize functional regulation of BACE1-AS in neurodegenerative diseases. This research proposal will put forward new strategies to investigate the specific mechanism of lncRNA in neurodegenerative diseases and provide new ideas and means for liquid biopsy and etiological treatment for neurodegenerative diseases.