AUTHOR=Dues Dylan J. , Moore Darren J. 

TITLE=LRRK2 and Protein Aggregation in Parkinson’s Disease: Insights From Animal Models

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00719

DOI=10.3389/fnins.2020.00719

ISSN=1662-453X

ABSTRACT=<p>Mutations in <italic>leucine-rich repeat kinase 2</italic> (<italic>LRRK2</italic>) instigate an autosomal dominant form of Parkinson’s disease (PD). Despite the neuropathological heterogeneity observed in <italic>LRRK2</italic>-PD, accumulating evidence suggests that alpha-synuclein and tau pathology are observed in a vast majority of cases. Intriguingly, the presence of protein aggregates spans both <italic>LRRK2</italic>-PD and idiopathic disease, supportive of a common pathologic mechanism. Thus, it is important to consider how LRRK2 mutations give rise to such pathology, and whether targeting LRRK2 might modify the accumulation, transmission, or toxicity of protein aggregates. Likewise, it is not clear how LRRK2 mutations drive PD pathogenesis, and whether protein aggregates are implicated in LRRK2-dependent neurodegeneration. While animal models have been instrumental in furthering our understanding of a potential interaction between LRRK2 and protein aggregation, the biology is far from clear. We aim to provide a thoughtful overview of the evidence linking LRRK2 to protein aggregation in animal models.</p>