二价金属离子在朊蛋白致病机理中的作用

Role of divalent metal ions in prion pathogenesis:a review

介绍了朊病毒(PrPSc)与动物体内正常朊蛋白(PrPC)的构象转化关系,重点阐述了PrPC氨基端的八肽重复区与一些金属离子的结合与其构象转化和致病性密切相关。综述了二价金属离子Cu2+、Zn2+、Ca2+、Ni 2+、Mn2+和Fe2+对朊蛋白结构和功能的影响,以及它们在朊病毒病发病机理中的可能作用。同时,这些二价金属离子还与PrPC的抗氧化应激有关,可以减轻疾病过程中脑组织的氧化损伤;而且PrPC对脑组织中二价金属离子的代谢也有一定的调节作用。

The association of conformational changes between prion（PrP^sc） and animals normal prion （PrP^c） were introduced. The octar repeat region is present within the N-terminal and is considered to be main metal ions-binding sites on prion. The binding is closely related with the conformational conversion of PrPc and its virulence. Especially,the influence of the divalent metal ions,such as Cu^2＋ ,Zn^2＋ ,Ca^2＋,Ni^2＋, Mn^2＋ and Fe^2＋ ,on structure and function of prion,as well as their possible roles in the pathogenesis of pri-on disease were discussed. Besides,PrP^c is an antioxidant proteins,and its antioxidant activity is associated with these metal ions. The interaction between the expression of PrP^c and the homeostais of different diva-lent metal ions were proposed.