我们和其他研究证实，在椎间盘退变（IDD）过程中，β-淀粉样蛋白hIAPP异常聚积导致髓核细胞（NPCs）线粒体损伤和自噬功能障碍，加速椎间盘损伤与退变；而PINK1/Parkin信号通路能够增强线粒体自噬，促进受损的线粒体的清除，维持细胞内部环境相对稳定。据此我们推测，hIAPP聚积导致PINK1/Parkin介导的线粒体自噬功能障碍，在IDD发病机制中扮演重要角色；通过该通路激活线粒体自噬，能够减轻hIAPP聚积所致线粒体损伤与功能紊乱，是IDD致病重要调节机制之一。本研究拟通过临床标本测定、细胞实验和动物模型研究，以hIAPP聚集体诱导髓核细胞损伤为切入点，阐明PINK1/Parkin介导的线粒体自噬功能障碍在椎间盘退变的作用及机制，并探究hIAPP聚积与IDD的相关性。本研究有望揭示IDD精确分子机制、设计靶向治疗药物、探索IDD生物学治疗新方法。

Our and other studies have confirmed that β-amyloid deposition of human islet amyloid polypeptide (hIAPP) lead to dysfunctional and abnormal of autophagy and mitochondrial function in nucleus pulposus cells (NPCs) during intervertebral disc degeneration (IDD), eventually resulted in disc degeneration or injury.PINK1/Parkin-dependent mechanism can enhance mitochondrial autophagy and promote the clearance of damaged mitochondria.Therefore, we hypothesized that hIAPP aggregation resulted in PINK1/Parkin mediated mitophagy inhibition, which was a novel mechanism of IDD.Mitochondrial damage and dysfunction caused by hIAPP aggregation could be alleviated through the activation of PINK1/Parkin medicated mitochondrial autophagy, which is one of the important regulatory mechanisms of IDD pathogenesis. Based on the latest literatures and our previous research, this study takes NPCs degeneration induced by hIAPP aggregation as the breakthrough point, to elucidate the role and mechanism of PINK1/Parkin mediated mitophagy inhibition in IDD, and to explore the relationship between hIAPP aggregation and IDD. It’s of groundbreaking significance to reveal the precise molecular mechanism, design targeted therapeutic drugs and explore biological treatment methods for IDD.