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

AbstractMutations 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 betweenLRRK2-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 ofLRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from differentLRRK2 KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research