Taymans Jean-Marc, Fell Matt, Greenamyre Tim, Hirst Warren D, Mamais Adamantios, Padmanabhan Shalini, Peter Inga, Rideout Hardy, Thaler Avner
Univ. Lille, Inserm, CHU Lille, UMR-S 1172-LilNCog-Lille Neuroscience & Cognition, F-59000, Lille, France.
Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA, 02115, USA.
NPJ Parkinsons Dis. 2023 Jul 1;9(1):104. doi: 10.1038/s41531-023-00544-7.
Almost 2 decades after linking LRRK2 to Parkinson's disease, a vibrant research field has developed around the study of this gene and its protein product. Recent studies have begun to elucidate molecular structures of LRRK2 and its complexes, and our understanding of LRRK2 has continued to grow, affirming decisions made years ago to therapeutically target this enzyme for PD. Markers of LRRK2 activity, with potential to monitor disease progression or treatment efficacy, are also under development. Interestingly, there is a growing understanding of the role of LRRK2 outside of the central nervous system in peripheral tissues such as gut and immune cells that may also contribute to LRRK2 mediated pathology. In this perspective, our goal is to take stock of LRRK2 research by discussing the current state of knowledge and critical open questions in the field.
在将亮氨酸重复激酶2(LRRK2)与帕金森病联系起来近20年后,围绕该基因及其蛋白质产物的研究形成了一个活跃的研究领域。最近的研究已开始阐明LRRK2及其复合物的分子结构,并且我们对LRRK2的理解持续加深,这证实了多年前做出的针对该酶治疗帕金森病的决定。具有监测疾病进展或治疗效果潜力的LRRK2活性标志物也在开发中。有趣的是,人们越来越了解LRRK2在中枢神经系统之外的肠道和免疫细胞等外周组织中的作用,这也可能导致LRRK2介导的病理变化。从这个角度来看,我们的目标是通过讨论该领域的当前知识状态和关键的未解决问题来总结LRRK2的研究情况。