LRRK2激酶在帕金森病中的致病机制及相关抑制剂的研发进展

The Development of Inhibitors of Leucine-rich Repeat Kinase 2 as a Therapeutic Strategy for Parkinson’s Disease

目前帕金森病(PD)治疗的主要方法是以改善运动症状为核心的多巴胺替代治疗,但潜在的疾病进程难以被打断或者延缓。随着PD遗传研究的跨越式发展,一系列单基因突变和患病风险位点被陆续发现,疾病发生发展的分子机制得以进一步阐明,也为PD患者个体化治疗奠定了理论基础。PD相关基因LRRK2作为潜在治疗靶点,受到广泛关注。文中旨在对LRRK2基因的结构功能、致病机制、最新治疗研究进展进行综述。

Current therapeutic approaches for Parkinson’s disease(PD) are based around dopamine replacement therapy that alleviates motor symptoms,but does not slow or prevent disease progression.Following the identification of monogenic causes and a plethora of risk loci for PD,the molecular mechanism of disease development has been further elucidated,which makes it possible to individualize the treatment for patients with PD.A promising approach is the use of molecules that inhibit the function of leucine-rich repeat kinase(LRRK 2).The physiological function,pathogenic mechanism,and recent therapeutic progress of LRRK 2 gene were reviewed.