Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-3707, USA.
Expert Rev Mol Med. 2011 Jun 13;13:e20. doi: 10.1017/S146239941100192X.
Parkinson disease is a common and usually sporadic neurodegenerative disorder. However, a subset of cases are inherited and, of these, mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of disease. Here, we will discuss recent progress in understanding how LRRK2 mutations lead to disease and how this might have therapeutic implications. The effect of mutations on LRRK2 enzyme function provides clues as to which functions of the protein are important to disease. Recent work has focused on the kinase and GTP-binding domains of LRRK2, and it is assumed that these will be therapeutically important, although there is a substantial amount of work to be done to address this hypothesis.
帕金森病是一种常见且通常为散发性的神经退行性疾病。然而，有一部分病例是遗传性的，在这些遗传性病例中，编码富含亮氨酸重复激酶 2（LRRK2）的基因突变是最常见的遗传病因。在这里，我们将讨论在理解 LRRK2 突变如何导致疾病方面的最新进展，以及这可能具有的治疗意义。突变对 LRRK2 酶功能的影响为我们提供了线索，说明该蛋白的哪些功能对疾病很重要。最近的工作集中在 LRRK2 的激酶和 GTP 结合结构域上，人们认为这些结构域在治疗上很重要，尽管还有大量的工作要做才能验证这一假设。
