LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson’s disease  

作　　者：Eunice Eun Seo Chang Philip Wing-Lok Ho Hui-Fang Liu Shirley Yin-Yu Pang Chi-Ting Leung Yasine Malki Zoe Yuen-Kiu Choi David Boyer Ramsden Shu-Leong Ho 

机构地区：[1]Division of Neurology,Department of Medicine,Queen Mary Hospital,University of Hong Kong,Pok Fu Lam,Hong Kong,China [2]Institute of Metabolism and Systems Research,University of Birmingham,Birmingham,UK.

出　　处：《Translational Neurodegeneration》2022年第1期790-808,共19页转化神经变性病（英文）

基　　金：Tai Hung Fai Charitable Foundation-Edwin S H Leong Research Programme for Parkinson’s Disease;The Henry G.Leong Endowed Professorship in Neurology;The Donation Fund for Neurology Research;Health and Medical Research Fund(HMRF),Food and Health Bureau,Hong Kong S.A.R.

摘　　要：Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a thera-peutic target in PD. LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use of LRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from different LRRK2 KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.

关 键 词：Parkinson’s disease LRRK2 Knock-in mouse model NEUROTRANSMISSION Motor dysfunction Autophagy LYSOSOME Mitochondrial dysfunction SYNUCLEINOPATHY Hyperkinase activity LRRK2 inhibitor 

分 类 号：R742.5[医药卫生—神经病学与精神病学]