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Models of LRRK2-Associated Parkinson’s Disease

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Leucine-Rich Repeat Kinase 2 (LRRK2)

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 14))

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic causes of Parkinson’s disease (PD) and also one of the strongest genetic risk factors in sporadic PD. The LRRK2 protein contains a GTPase and a kinase domain and several protein-protein interaction domains. Both in vitro and in vivo assays in different model systems have provided tremendous insights into the molecular mechanisms underlying LRRK2-induced dopaminergic neurodegeneration. Among all the model systems, animal models are crucial tools to study the pathogenesis of human disease. How do the animal models recapitulate LRRK2-induced dopaminergic neuronal loss in human PD? To answer this question, this review focuses on the discussion of the animal models of LRRK2-associated PD including genetic- and viral-based models.

Funding for a portion of Dr. Dawson’s LRRK2 research in the past was provided by Merck KGAA. Under a licensing agreement between Merck KGAA and the Johns Hopkins University, Dr. Dawson and the University shared fees received by the University on licensing some of the reagents used in his research. Dr. Dawson also was a paid consultant to Merck KGAA.

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Acknowledgments

This work was supported by grants from the NIH/NINDS NS38377 (VLD and TMD), the JPB Foundation (TMD), NIH/NIA K01-AG046366 (YX), and the William N. & Bernice E. Bumpus Foundation Innovation Awards (YX). TMD is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. The authors acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with the Johns Hopkins Hospital and the Johns Hopkins University School of Medicine and the Foundation’s Parkinson’s Disease Programs, M-1, M-2.

Conflict of Interest

The author declares no conflicts of interest.

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Authors and Affiliations

  1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Yulan Xiong, Ted M. Dawson & Valina L. Dawson

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Yulan Xiong, Ted M. Dawson & Valina L. Dawson

  3. Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, 66506, USA

    Yulan Xiong

  4. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Ted M. Dawson

  5. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Ted M. Dawson & Valina L. Dawson

  6. Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, 70130-2685, USA

    Ted M. Dawson & Valina L. Dawson

  7. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Valina L. Dawson

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  1. Yulan Xiong
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  2. Ted M. Dawson
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  3. Valina L. Dawson
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Corresponding authors

Correspondence to Yulan Xiong , Ted M. Dawson or Valina L. Dawson .

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  1. Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece

    Hardy J. Rideout

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Xiong, Y., Dawson, T.M., Dawson, V.L. (2017). Models of LRRK2-Associated Parkinson’s Disease. In: Rideout, H. (eds) Leucine-Rich Repeat Kinase 2 (LRRK2). Advances in Neurobiology, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-49969-7_9

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