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Small-Molecule Inhibitors of LRRK2

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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) protein have been genetically and functionally linked to Parkinson’s disease (PD). The kinase activity of LRRK2 is increased by pathogenic mutations; therefore, modulation of LRRK2 kinase activity by a selective small-molecule inhibitor has been proposed as a potentially viable treatment for Parkinson’s disease. This chapter presents a historical overview of the development and bioactivity of several small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or in vivo. These compounds are important tools for understanding the cellular biology of LRRK2 and for evaluating the potential of LRRK2 inhibitors as disease-modifying PD therapies.

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Conflict of Interest

The author declares no conflicts of interest.

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Authors and Affiliations

  1. Department of Cancer Biology, Dana Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA

    John M. Hatcher & Nathanael S. Gray

  2. New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, 80 Cheombok-ro, Dong-gu, Daegu, 41061, South Korea

    Hwan Geun Choi

  3. MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK

    Dario R. Alessi

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  1. John M. Hatcher
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  2. Hwan Geun Choi
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  3. Dario R. Alessi
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  4. Nathanael S. Gray
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Correspondence to Nathanael S. Gray .

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Editors and Affiliations

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

    Hardy J. Rideout

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Hatcher, J.M., Choi, H.G., Alessi, D.R., Gray, N.S. (2017). Small-Molecule Inhibitors of LRRK2. 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_13

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