帕金森病研究中LRRK2激酶抑制剂的进展  

LRRK2 kinase inhibitors for Parkinson's disease

作　　者：王林[1] 杨洁[1] 杜磊[1] 孙铁民[1] 

机构地区：[1]沈阳药科大学创新药物研究与设计教育部重点实验室,沈阳110016

出　　处：《中南药学》2015年第10期1009-1016,共8页Central South Pharmacy

基　　金：教育部创新团队发展计划;辽宁省高校创新团队支持资助

摘　　要：帕金森病严重危害老年人的生活质量和健康。其典型表征是脑内黑质中多巴胺能神经元的减少,从而导致的临床表现为动作迟缓、静止震颤、肌强直和姿势步态障碍。多数的帕金森氏病是先天的,并发现通过基因遗传。LRRK2基因突变是帕金森病（PD）的重要病因。在超过65岁的人群中,有1%~2%的老年人患有帕金森病。为了寻找有效治疗帕金森的治疗方案,众多药学科研者致力于研究LRRK2激酶抑制剂。从发现LRRK2激酶到现在的十多年里,药学研究者发现了一大批高效、高选择的LRRK2激酶抑制剂,尽管可能成药的抑制剂尚在研究中。本文对LRRK2激酶抑制剂的研究现状进行综述,以引起人们对LRRK2激酶抑制剂的关注。Parkinson＇s disease （PD） seriously endangers the quality of life and health of the elderly. The most common phenotype of PD is the loss of dopaminergic neurons in the substantia nigra resulting in bradykinesia, resting tremors,rigidity, and postural instability. The predominant form of the disease is idiopathic, but a genetic disposition to PD has been observed. The most common genetic cause of autosomal dominant PD is mutations in leucine-rich repeat kinase 2 （LRRK2）. Among the over 65 year-olds, approximately 1% -- 2% suffer from PD. To find safe and potent treat- ment programs of PD, many researchers focus on LRRK2 kinase inhibitors. In the last 20 years after the discovery of LRRK2, many potent and selective LRRK2 kinases were discovered, and some drug-like inhibitors are still develop- ing. This paper reviews the research of LRRK2 kinase inhibitors.

关 键 词：帕金森 基因突变 LRRK2激酶:LRRK2激酶抑制剂 

分 类 号：R363[医药卫生—病理学]