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

Eunice Eun Seo Chang, Philip Wing Lok Ho (Corresponding Author), Hui Fang Liu, Shirley Yin Yu Pang, Chi Ting Leung, Yasine Malki, Zoe Yuen Kiu Choi, David Boyer Ramsden, Shu Leong Ho (Corresponding Author)

Research output: Journal article publicationReview articleAcademic researchpeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Article number10
JournalTranslational Neurodegeneration
Issue number1
Publication statusPublished - 14 Feb 2022


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

ASJC Scopus subject areas

  • Clinical Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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