非编码RNA在脑衰老向阿尔茨海默病演进中的作用与机制研究

非编码RNA（ncRNA）在进化中伴随认知等复杂行为出现并大规模扩增，40%的ncRNA在脑中特异性表达。已知ncRNA参与学习记忆等脑功能调控，但ncRNA在脑衰老以及阿尔茨海默病中的作用并不清楚。我们提出假设，脑衰老中ncRNA的异常引起认知相关神经网络或功能改变，进而引起神经退行性改变，导致阿尔茨海默病。本研究将利用细胞和动物模型来深入研究：1.ncRNA在脑衰老中的作用及分子机制；2.脑衰老中ncRNA异常与阿尔茨海默病的内在关系；3.利用代谢组学等方法研究ncRNA异常导致的代谢改变，筛选和发现新的生物标志物。通过单细胞测序，发现衰老过程中发生细胞类型特异改变的ncRNA,揭示ncRNA在衰老向阿尔茨海默病转变过程中的关键调控网络，解析ncRNA作为衰老向阿尔茨海默病转变的分子标志物与临床干预靶标的可行性，提供基于ncRNA的全新治疗方案。

Non-coding RNA (ncRNA) are rapidly expanding along with the acquisition of complex behavioral capacities such as learning and memory during evolution； approximately 40% of these ncRNAs are specifically expressed in the brain. ncRNA is critical for regulation of cognitive function, however, the role of ncRNA in brain aging and Alzheimer’s disease remains elusive. We hypothesize that abnormal ncRNA expression/function during brain aging processes leads to neuronal dysfunctional, contributing to neurodegenerative processes and the pathogenesis of Alzheimer’s disease. Based on our previous studies, we will utilize cellular and animal models to study: 1.the molecular and cellular mechanisms by which ncRNA functions in brain aging; 2.the inter-relationship between brain aging induced-ncRNA change and Alzheimer’s disease; 3. Using metabolomics to study how abnormal ncRNA leads to metabolic changes during brain aging and Alzheimer’s disease, and screen for new biomarkers. We will also utilize single cell sequencing to screen for ncRNAs whose expressions change differentially in specific cell type during brain aging. Our study shall discover the ncRNA regulatory network which plays a critical role during the shift or transition from brain aging to Alzheimer’s disease pathological process. In addition, our investigation will identify the potential ncRNA biomarkers and therapeutic targets for the shift from aging-related neurological disorders including Alzheimer’s disease.