School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
J Physiol. 2019 Jul;597(14):3511-3521. doi: 10.1113/JP276163. Epub 2019 Jun 11.
The LRRK2 gene, coding for leucine rich repeat kinase 2 (LRRK2), is a key player in the genetics of Parkinson's disease. Despite extensive efforts, LRRK2 has proved remarkably evasive with regard to attempts to understand both the role it plays in disease and its normal physiological function. At least part of why LRRK2 has been so difficult to define is that it appears to be many things to many cellular functions and diseases - a pleiotropic actor at both the genetic and the molecular level. Gaining greater insight into the mechanisms and pathways allowing LRRK2 to act in this manner will have implications for our understanding of the role of genes in the aetiology of complex disease, the molecular underpinnings of signal transduction pathways in the cell, and drug discovery in the genome era.
LRRK2 基因，编码富含亮氨酸重复激酶 2（LRRK2），是帕金森病遗传学中的关键因素。尽管进行了广泛的研究，但 LRRK2 在理解其在疾病中的作用及其正常生理功能方面一直非常难以捉摸。LRRK2 之所以如此难以定义的部分原因是，它似乎在遗传和分子水平上对许多细胞功能和疾病都具有多种作用——是一种多效性的因子。深入了解允许 LRRK2 以这种方式发挥作用的机制和途径，将有助于我们理解基因在复杂疾病发病机制中的作用、细胞内信号转导途径的分子基础，以及基因组时代的药物发现。
