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

Translational Neurodegeneration

Zoe Yuen-Kiu Choi¹  Shu-Leong Ho¹  Philip Wing-Lok Ho¹  Shirley Yin-Yu Pang¹  Chi-Ting Leung¹  Yasine Malki¹  Hui-Fang Liu¹  Eunice Eun Seo Chang¹  David Boyer Ramsden² 

[1] Division of Neurology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pok Fu Lam, Hong Kong, China;Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK;

关键词: Parkinson’s disease;    LRRK2;    Knock-in mouse model;    Neurotransmission;    Motor dysfunction;    Autophagy;    Lysosome;    Mitochondrial dysfunction;    Synucleinopathy;    Hyperkinase activity;    LRRK2 inhibitor;   

DOI  :  10.1186/s40035-022-00285-2

来源: Springer

【 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 therapeutic 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.

【 授权许可】

CC BY