Long Olivia S, Gosai Sager J, Kwak Joon Hyeok, King Dale E, Perlmutter David H, Silverman Gary A, Pak Stephen C
Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh of UPMC, Pittsburg, Pennsylvania, USA.
Methods Enzymol. 2011;499:259-81. doi: 10.1016/B978-0-12-386471-0.00013-4.
Protein misfolding, polymerization, and/or aggregation are hallmarks of serpinopathies and many other human genetic disorders including Alzheimer's, Huntington's, and Parkinson's disease. While higher organism models have helped shape our understanding of these diseases, simpler model systems, like Caenorhabditis elegans, offer great versatility for elucidating complex genetic mechanisms underlying these diseases. Moreover, recent advances in automated high-throughput methodologies have promoted C. elegans as a useful tool for drug discovery. In this chapter, we describe how one could model serpinopathies in C. elegans and how one could exploit this model to identify small molecule compounds that can be developed into effective therapeutic drugs.
蛋白质错误折叠、聚合和/或聚集是丝氨酸蛋白酶抑制剂病以及包括阿尔茨海默病、亨廷顿病和帕金森病在内的许多其他人类遗传疾病的标志。虽然高等生物模型有助于我们理解这些疾病,但更简单的模型系统,如秀丽隐杆线虫,在阐明这些疾病背后的复杂遗传机制方面具有很大的通用性。此外,自动化高通量方法的最新进展推动了秀丽隐杆线虫成为药物发现的有用工具。在本章中,我们描述了如何在秀丽隐杆线虫中模拟丝氨酸蛋白酶抑制剂病,以及如何利用该模型鉴定可开发成有效治疗药物的小分子化合物。