二硫键异构酶在神经变性疾病中的调控机制

Regulating mechanism of protein-disulphide isomerase in neurodegenerative diseases

二硫键异构酶(protein-disulphide isomerase,PDI)作为巯基-二硫键交换反应的催化剂,可促进蛋白二硫键的生成和错配二硫键的重排;同时它具有分子伴侣活性,能抑制错误折叠蛋白的聚集。在神经变性疾病如帕金森症、阿尔兹海默症、肌萎缩侧索硬化症、多聚谷氨酰胺疾病中,PDI可通过抑制错误折叠蛋白的聚集以及遍在蛋白化,起到神经保护作用。但是PDI能被过量的一氧化氮亚硝基化,导致其蛋白质构象改变和功能障碍,影响神经元的连通性和可塑性,触发神经元的凋亡通路。本文就最新研究综述了PDI的结构功能、调控机制及在神经变性疾病的作用。

Protein-disulphide isomerase（PDI） , as a catalyst of the thiol-disulfide exchange, can facilitate disulfide bond formation and mismatched disulfide bond rearrangement reactions in proteins. At the same time, PDI can act as molecular chaperone that help the denatured proteins refold and inhibit the aggregation of the denatured proteins. A common histological characteristics of many neurodegenerative diseases such as Parkinson＇ s disease, Alzheimer＇ s disease, amyotrophic lateral sclerosis, and polyglu- tamine diseases is the accumulation of misfolded proteins, but the upregulation of PDI during neurodegen- erative diseases represents an adaptive response to neuronal cells protection. PDI could be S-nitrosylated by excessive nitric oxide, which can induce the conformational changes and dysfunction of PDI. The S- nitrosylateion affects the neuronal connectivity and plasticity, and triggers cell death signaling pathways. In this review, we will discuss the structure and functions of PDI as well as its mechanism. Furthermore, we reveal the relation between PDI and the neurodegenerative diseases according to the recent research.