Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, United Kingdom.
J Biol Chem. 2010 Apr 9;285(15):11061-7. doi: 10.1074/jbc.R109.072181. Epub 2010 Feb 10.
Many of the neurodegenerative diseases that afflict people are caused by intracytoplasmic aggregate-prone proteins. These include Parkinson disease, tauopathies, and polyglutamine expansion diseases such as Huntington disease. In Mendelian forms of these diseases, the mutations generally confer toxic novel functions on the relevant proteins. Thus, one potential strategy for dealing with these mutant proteins is to enhance their degradation. This can be achieved by up-regulating macroautophagy, which we will henceforth call autophagy. In this minireview, we will consider the reasons why autophagy up-regulation may be a powerful strategy for these diseases. In addition, we will consider some of the drugs and associated signaling pathways that can be used to induce autophagy with these therapeutic aims in mind.
许多困扰人类的神经退行性疾病是由细胞浆内易于聚集的蛋白质引起的。这些疾病包括帕金森病、tau 病和亨廷顿病等多聚谷氨酰胺扩展疾病。在这些疾病的孟德尔形式中，突变通常会赋予相关蛋白质有毒的新功能。因此，处理这些突变蛋白的一种潜在策略是增强它们的降解。这可以通过上调巨自噬来实现，我们将其简称为自噬。在这篇综述中，我们将考虑自噬上调可能成为这些疾病的强大治疗策略的原因。此外，我们还将考虑一些可用于诱导自噬的药物和相关信号通路，以实现这些治疗目的。
