Genetic LRRK2 models of Parkinson's disease: Dissecting the pathogenic pathway and exploring clinical applications

Authors

  • Zhenyu Yue PhD,

    Corresponding author
    1. Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA
    • Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
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  • M. Lenard Lachenmayer MD

    1. Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Neurology, University of Bonn, Bonn, Germany
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  • Funding agencies: This work was supported by NIH/NINDS grants NS060809-01 and NS072359-01 and the Michael J. Fox Foundation for Parkinson's Research.

    Relevant conflicts of interest/financial disclosures: Nothing to report.

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Dominantly inherited mutations in leucine-rich repeat kinase 2 are the most common cause of familial Parkinson's disease. Understanding leucine-rich repeat kinase 2 biology and pathophysiology is central to the elucidation of Parkinson's disease etiology and development of disease intervention. Recently, a number of genetic mouse models of leucine-rich repeat kinase 2 have been reported utilizing different genetic approaches. Some similarities in Parkinson's disease-related pathology emerge in these genetic models despite lack of substantial neuropathology and clinical syndromes of Parkinson's disease. The systematic characterization of these models has begun to shed light on leucine-rich repeat kinase 2 biology and pathophysiology and is expected to offer the identification and validation of drug targets. In this review, we summarize the progress of genetic leucine-rich repeat kinase 2 mouse models and discuss their utility in understanding much needed knowledge regarding early-stage (presymptomatic) disease progression, identifying drug targets, and exploring the potential to aid compound screening focused on inhibitors of kinase activity of leucine-rich repeat kinase 2. © 2011 Movement Disorder Society

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