Kinases as Targets for Parkinson's Disease: From Genetics to Therapy

被引：34

作者：

Vancraenenbroeck, Renee ^{[1
]}

Lobbestael, Evy ^{[2
]}

De Maeyer, Marc ^{[1
]}

Baekelandt, Veerle ^{[2
]}

Taymans, Jean-Marc ^{[2
]}

机构：

[1] Katholieke Univ Leuven, Lab Biomol Modelling, Louvain, Belgium

[2] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium

来源：

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS | 2011年 / 10卷 / 06期

关键词：

Leucine rich repeat kinase 2; polo like kinase 2; alpha-synuclein; RICH REPEAT KINASE-2; PHOSPHORYLATES ALPHA-SYNUCLEIN; SMALL-MOLECULE INHIBITOR; RAT MODEL; DOPAMINERGIC-NEURONS; TRANSGENIC MICE; PROTEIN-KINASES; GTP-BINDING; ROC DOMAIN; DROSOPHILA MODEL;

D O I：

10.2174/187152711797247858

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Intense research efforts are currently directed at elucidating the etiology of Parkinson's disease (PD). One approach that has begun to shed light on the PD pathogenic pathways is the identification of disease genes through genetic linkage or association studies. These studies have revealed that several kinases may be involved in PD, as some PD genes encode kinases themselves while other PD genes are found in the same cellular pathways as kinases. Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (alpha-syn) phosphorylating polo-like kinase 2 (PLK2). Indeed, both alpha-syn and LRRK2 show genetic linkage as well as genetic association with PD, indicating their relevance to a large number of PD cases. Also, due to the dominant mode of alpha-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and alpha-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD. Here we discuss the function of these kinases as well as progress in their validation as drug targets for the treatment of PD.

引用

页码：724 / 740

页数：17

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