Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
J Transl Med. 2024 Aug 5;22(1):719. doi: 10.1186/s12967-024-05535-7.
With the increasing age of the population worldwide, the incidence rate of Parkinson's disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease. In the present study, whole transcriptome sequencing was used to obtain the mRNA and miRNA expression profiles in a PD mouse model, which revealed the pathogenesis of PD. The transcription factor RUNX3 upregulated the miR-186-3p expression in the PD model. Furthermore, the high miR-186-3p expression in PD can be targeted to inhibit the DAT expression, resulting in a decrease in the dopamine content of dopaminergic neurons. Moreover, miR-186-3p can be targeted to inhibit the IGF1R expression and prevent the activation of the IGF1R-P-PI3K-P-AKT pathway, thus increasing the apoptosis of dopaminergic neurons by regulating the cytochrome c-Bax-cleaved caspase-3 pathway. Our research showed that the RUNX3-miR-186-3p-DAT-IGF1R axis plays a key role in the pathogenesis of PD, and miR-186-3p is a potential target for the treatment of PD.
随着全球人口老龄化，帕金森病（PD）的发病率逐年上升。目前，PD 的治疗策略仅能改善临床症状，尚无有效的治疗策略能减缓疾病的进展。本研究通过全转录组测序获得 PD 小鼠模型中的 mRNA 和 miRNA 表达谱，揭示了 PD 的发病机制。转录因子 RUNX3 上调 PD 模型中的 miR-186-3p 表达。此外，PD 中高表达的 miR-186-3p 可靶向抑制 DAT 表达，导致多巴胺能神经元中多巴胺含量降低。此外，miR-186-3p 可靶向抑制 IGF1R 表达，阻止 IGF1R-P-PI3K-P-AKT 通路的激活，从而通过调节细胞色素 c-Bax-裂解的 caspase-3 通路增加多巴胺能神经元的凋亡。我们的研究表明，RUNX3-miR-186-3p-DAT-IGF1R 轴在 PD 的发病机制中起关键作用，miR-186-3p 是治疗 PD 的潜在靶点。
