SIMOPRO, Institute de Biologie et de Technologies de Saclay, DSV/CEA, Bat. 152, CE-Saclay, Gif-sur-Yvette Cedex, France.
Cell Mol Life Sci. 2010 Oct;67(20):3467-88. doi: 10.1007/s00018-010-0437-0. Epub 2010 Jul 4.
Cyclosporine A (CsA) is an immunosuppressive cyclic peptide that binds with a high affinity to 18 kDa human cyclophilin-A (hCyPA). CsA and its several natural derivatives have some pharmacological potential in treatment of diverse immune disorders. More than 20 paralogues of CyPA are expressed in the human body while expression levels and functions of numerous ORFs encoding cyclophilin-like sequences remain unknown. Certain derivatives of CsA devoid of immunosuppressive activity may have some potential in treatments of Alzheimer diseases, Hepatitis C and HIV infections, amyotrophic lateral sclerosis, congenital muscular dystrophy, asthma and various parasitic infections. Here, we discuss structural and functional aspects of the human cyclophilins and their interaction with various intra-cellular targets that can be under the control of CsA or its complexes with diverse cyclophilins that are selectively expressed in different cellular compartments. Some molecular aspects of the cyclophilins expressed in parasites invading humans and causing diseases were also analyzed.
环孢素 A（CsA）是一种具有免疫抑制作用的环状肽，与 18 kDa 的人亲环蛋白 A（hCyPA）具有高亲和力结合。CsA 及其几种天然衍生物在治疗多种免疫疾病方面具有一定的药理学潜力。人体中表达了超过 20 种亲环蛋白的同源物，而编码亲环蛋白样序列的许多 ORF 的表达水平和功能仍然未知。某些无免疫抑制活性的 CsA 衍生物可能在治疗阿尔茨海默病、丙型肝炎和 HIV 感染、肌萎缩侧索硬化症、先天性肌营养不良症、哮喘和各种寄生虫感染方面具有一定的潜力。在这里，我们讨论了人类亲环蛋白的结构和功能及其与各种细胞内靶标的相互作用，这些靶标可以受到 CsA 或其与选择性表达在不同细胞区室中的各种亲环蛋白的复合物的控制。还分析了表达在入侵人体并导致疾病的寄生虫中的亲环蛋白的一些分子方面。
