Abstract
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 language | English |
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Article number | 10 |
Journal | Translational Neurodegeneration |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 14 Feb 2022 |
Keywords
- 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