Hegde Ramanath Narayana, Subramanian Advait, Pothukuchi Prathyush, Parashuraman Seetharaman, Luini Alberto
Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Tissue Cell. 2017 Apr;49(2 Pt A):175-185. doi: 10.1016/j.tice.2017.02.001. Epub 2017 Feb 9.
The presence of a functional protein at the appropriate location in the cell is the result of the processes of transcription, translation, folding and trafficking to the correct destination. There are numerous diseases that are caused by protein misfolding, mainly due to mutations in the respective gene. The consequences of this misfolding may be that proteins effectively lose their function, either by being removed by the cellular quality control machinery or by accumulating at the incorrect intracellular or extracellular location. A number of mutations that lead to protein misfolding and affect trafficking to the final destination, e.g. Cystic fibrosis, Wilson's disease, and Progressive Familial Intrahepatic 1 cholestasis, result in proteins that retain partial function if their folding and trafficking is restored either by molecular or pharmacological means. In this review, we discuss several mutant proteins within this class of misfolding diseases and provide an update on the status of molecular and therapeutic developments and potential therapeutic strategies being developed to counter these diseases.
细胞中功能性蛋白质在适当位置的存在是转录、翻译、折叠以及转运至正确目的地等过程的结果。有许多疾病是由蛋白质错误折叠引起的，主要原因是各自基因发生突变。这种错误折叠的后果可能是蛋白质有效地丧失其功能，要么被细胞质量控制机制清除，要么在细胞内或细胞外的错误位置积累。一些导致蛋白质错误折叠并影响其转运至最终目的地的突变，例如囊性纤维化、威尔逊氏病和进行性家族性肝内胆汁淤积症，如果通过分子或药理学手段恢复其折叠和转运，所产生的蛋白质仍保留部分功能。在本综述中，我们讨论了这类错误折叠疾病中的几种突变蛋白，并提供了分子和治疗进展的最新情况以及为对抗这些疾病而正在开发的潜在治疗策略。
