Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London NW1 0TU, UK.
Department of Neurodegenerative diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
J Cell Sci. 2023 Sep 1;136(17). doi: 10.1242/jcs.259724. Epub 2023 Sep 12.
Leucine-rich repeat kinase 2 (LRRK2) is a multidomain scaffolding protein with dual guanosine triphosphatase (GTPase) and kinase enzymatic activities, providing this protein with the capacity to regulate a multitude of signalling pathways and act as a key mediator of diverse cellular processes. Much of the interest in LRRK2 derives from mutations in the LRRK2 gene being the most common genetic cause of Parkinson's disease, and from the association of the LRRK2 locus with a number of other human diseases, including inflammatory bowel disease. Therefore, the LRRK2 research field has focused on the link between LRRK2 and pathology, with the aim of uncovering the underlying mechanisms and, ultimately, finding novel therapies and treatments to combat them. From the biochemical and cellular functions of LRRK2, to its relevance to distinct disease mechanisms, this Cell Science at a Glance article and the accompanying poster deliver a snapshot of our current understanding of LRRK2 function, dysfunction and links to disease.
富含亮氨酸重复激酶 2(LRRK2)是一种具有双重鸟苷三磷酸酶(GTPase)和激酶酶活性的多功能支架蛋白,使该蛋白具有调节多种信号通路和作为多种细胞过程关键介质的能力。LRRK2 基因中的突变是帕金森病最常见的遗传原因,LRRK2 基因座与许多其他人类疾病(包括炎症性肠病)相关联,这引起了人们对 LRRK2 的极大兴趣。因此,LRRK2 研究领域的重点是 LRRK2 与病理学之间的联系,目的是揭示潜在的机制,并最终找到针对这些机制的新疗法。本文和随附的海报从 LRRK2 的生化和细胞功能到其与不同疾病机制的相关性,概述了我们目前对 LRRK2 功能、功能障碍和与疾病的联系的理解。