Division of Functional Genomics, Research Center for Bioscience & Technology, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan.
Future Med Chem. 2013 Sep;5(13):1551-8. doi: 10.4155/fmc.13.123.
A growing body of evidence suggests that misfolding of a mutant protein followed by its aggregation or premature degradation in the endoplasmic reticulum is one of the main mechanisms that underlie inherited neurodegenerative diseases, including lysosomal storage diseases. Chemical or pharmacological chaperones are small molecules that bind to and stabilize mutant lysosomal enzyme proteins in the endoplasmic reticulum. A number of chaperone compounds for lysosomal hydrolases have been identified in the last decade. They have gained attention because they can be orally administrated, and also because they can penetrate the blood-brain barrier. In this article, we describe two chaperone candidates for the treatment of GM1-gangliosidosis. We also discuss the future direction of this strategy targeting other lysosomal storage diseases as well as protein misfolding diseases in general.
越来越多的证据表明，突变蛋白的错误折叠，随后在内质网中聚集或过早降解，是导致包括溶酶体贮积症在内的遗传性神经退行性疾病的主要机制之一。化学或药理学伴侣分子是一种小分子，它可以与内质网中的突变溶酶体酶蛋白结合并稳定它们。在过去的十年中，已经鉴定出许多溶酶体水解酶的伴侣化合物。它们受到关注是因为它们可以口服给药，也因为它们可以穿透血脑屏障。本文描述了两种用于治疗 GM1-神经节苷脂贮积症的伴侣分子候选物。我们还讨论了针对其他溶酶体贮积症以及一般的蛋白质错误折叠疾病的这一策略的未来方向。
