帕金森病(Parkinson's disease, PD)是中枢神经系统第二大退行性病，以中脑黑质多巴胺能神经元进行性丢失为特征，目前仍缺乏非常有效的诊治手段。MicroRNA在PD病理机制中具有重要作用。MicroRNA29家族包括两个基因簇miR-29a/b1与b2/c，其在脑内的功能尚未明确。前期我们发现在PD病人的血清中miR-29s含量显著降低；MPP+处理的多巴胺能细胞中miR-29s表达亦明显下降；而在LPS处理的小胶质细胞内miR-29s表达则显著上升，提示miR-29s可能通过调节神经元凋亡和胶质细胞激活参与了PD；我们进而构建了miR-29a/b1与b2/c基因缺失突变的小鼠和细胞系。本申请拟利用这些模型并结合临床样本进一步阐明miR-29s在脑内的功能及在PD发病中的作用和机制，探讨血液中miR-29s含量作为PD发病的生物标志物的可行性，为PD的诊治提供新的思路。

Parkinson's disease is the second most common neurodegenerative disease, characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. There is still a lack of effective diagnosis and treatments for PD at yet. With research advances in PD, MicroRNA has been proved to play an important role in PD pathology. MicroRNA29 family (miR29s) is including two gene clusters: miR-29a/b1 and miR-29b2/c, which is widely expressed in the central nervous system (CNS). It has been recognized that there exists a closely relationship between miR29s and neurodegenerative diseases, but the specific mechanisms remain to be established. In our previous studies, we found that the levels of miR29s markedly decreased in the serum of PD patients; In a cellular PD model, MPP+ significantly reduced the expression of miR29s; However, miR29s increased dramatically in LPS-treated BV2 cells, indicating that miR29s might be involved in PD by the regulation of neuronal apoptosis and the activation of glial cells. In addition, the miR-29a/b1 and miR-29b2/c gene deficient mice and cell lines have been generated. In this project, we will decipher the physiological functions of miR29s in the brain and demonstrate the functions and mechanisms of miR29s in PD. Additionally, the possibility of miR29s in serum as a biomarker of PD and PD HY scales will be determined. Our work might provide new diagnostic and therapeutic alterations for PD.