自噬障碍是帕金森病（PD）关键发病因素。申请人前期报道，增强孤儿核受体Nur77出核可改善DA能神经元自噬障碍，但上游机制未明。研究表明，IGFBP3是调控Nur77出核的关键分子。我们前期运用基因芯片筛选发现PD患者血清lncRNA NBAT-1显著降低，lncRNA NBAT-1过表达可上调IGFBP3水平，促进Nur77出核，改善DA能神经元自噬障碍。进一步预实验：lncRNA NBAT-1可募集hnRNPU和DOT1L并锚定至IGFBP3启动子区域，通过DOT1L上调IGFBP3表达，促进Nur77出核。据此我们提出假说“lncRNA NBAT-1通过hnRNPU/DOT1L复合体上调IGFBP3表达，促进Nur77出核，改善DA能神经元自噬障碍”，从表观遗传新视角阐明lncRNA NBAT-1参与PD的发病机制，构建lncRNA对PD自噬的精细调控网络，为PD防治提供新靶点。

Autophagic dysfunction plays crucial roles in the pathogenesis of Parkinson's disease (PD). Our previous studies have revealed that upregulating the nuclear export of the orphan nuclear receptor Nur77 could improve autophagic dysfunction in DAergic neurons of PD. However, the exact upstream regulatory mechanism still remains unclear. Previous Studies have shown that IGFBP3 is a key molecule that regulates the nuclear export of Nur77. Results of microassay of long non-coding RNAs (lncRNAs) showed that lncRNA NBAT-1 was significantly downregulated in the plasma of PD patients compared with healthy control group. Moreover, overexpression of lncRNA NBAT-1 upregulated IGFBP3 expression and promoted the nuclear export of Nur77, subsequently improving DAergic neuronal degeneration. Further preliminary experiments found that: mechanistically, overexpression of lncRNA NBAT-1 recruited hnRNPU and DOT1L and then bound specifically to the IGFBP3 promoter to activate IGFBP3 transcription via increasing the methylation of histone，finally promoting the nuclear export of Nur77. Based on these, we propose the hypothesis that lncRNA NBAT-1 cooperated with hnRNPU/DOT1L complex induces autophagy in DAergic neurons of Parkinson's Disease through upregulating IGFBP3 expression and promoting the nuclear export of Nur77. We deeply explore the epigenetics mechanism of lncRNA NBAT-1 in the pathogenesis of PD, and constitute a delicate regulatory network for lncRNA in the modulation of autophagy, and provide new ideas for the prevention and treatment of PD.