Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jul 8:14:719.
doi: 10.3389/fnins.2020.00719. eCollection 2020.

LRRK2 and Protein Aggregation in Parkinson's Disease: Insights From Animal Models

Dylan J Dues  1 , Darren J Moore  1
Affiliations
Review

LRRK2 and Protein Aggregation in Parkinson's Disease: Insights From Animal Models

Dylan J Dues et al. Front Neurosci. .

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) instigate an autosomal dominant form of Parkinson's disease (PD). Despite the neuropathological heterogeneity observed in LRRK2-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 LRRK2-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.

Keywords: LRRK2; Parkinson’s disease; alpha-synuclein; animal models; neurodegeneration; protein aggregation; tau.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aarsland D., Perry R., Brown A., Larsen J. P., Ballard C. (2005). Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann. Neurol. 58 773–776. 10.1002/ana.20635 - DOI - PubMed
    1. Andersen M. A., Christensen K. V., Badolo L., Smith G. P., Jeggo R., Jensen P. H., et al. (2018). Parkinson’s disease-like burst firing activity in subthalamic nucleus induced by AAV-α-synuclein is normalized by LRRK2 modulation. Neurobiol. Dis. 116 13–27. 10.1016/j.nbd.2018.04.011 - DOI - PubMed
    1. Andersen M. A., Sotty F., Jensen P. H., Badolo L., Jeggo R., Smith G. P., et al. (2019). Long-term exposure to PFE-360 in the AAV-α-synuclein rat model: findings and implications. eNeuro 6: ENEURO.0453-18.2019. 10.1523/eneuro.0453-18.2019 - DOI - PMC - PubMed
    1. Bailey R. M., Covy J. P., Melrose H. L., Rousseau L., Watkinson R., Knight J., et al. (2013). LRRK2 phosphorylates novel tau epitopes and promotes tauopathy. Acta Neuropathol. 126 809–827. 10.1007/s00401-013-1188-4 - DOI - PMC - PubMed
    1. Berwick D. C., Heaton G. R., Azeggagh S., Harvey K. (2019). LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same. Mol. Neurodegener. 14: 49. 10.1186/s13024-019-0344-2 - DOI - PMC - PubMed

LinkOut - more resources