Small-Molecule Inhibitors of LRRK2

John M. Hatcher; Hwan Geun Choi; Dario R. Alessi; Nathanael S. Gray

doi:10.1007/978-3-319-49969-7_13

Small-Molecule Inhibitors of LRRK2

John M. Hatcher, Hwan Geun Choi, Dario R. Alessi, Nathanael S. Gray (Lead / Corresponding author)

MRC PPU

Research output: Chapter in Book/Report/Conference proceeding › Chapter (peer-reviewed) › peer-review

23 Citations (Scopus)

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.

Original language	English
Title of host publication	Leucine-Rich Repeat Kinase 2 (LRRK2)
Editors	Hardy J. Rideout
Publisher	Springer International Publishing
Pages	241-264
Number of pages	24
ISBN (Electronic)	9783319499697
ISBN (Print)	9783319499673
DOIs	https://doi.org/10.1007/978-3-319-49969-7_13
Publication status	Published - 2017

Publication series

Name	Advances in neurobiology
Publisher	Springer International Publishing
Volume	14
ISSN (Print)	2190-5215

Keywords

Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2)
LRRK2 inhibitors
Mutations

Access to Document

10.1007/978-3-319-49969-7_13

Towards a Unifying Theory of Parkinson's Disease - Investigation of the Biochemical and Genetic Role of Rab GTPases (joint with German Centre for Neurodegenerative Diseases)
Alessi, D. & Muqit, M.
Medical Research Council
17/10/16 → 16/10/18
Project: Research

Cite this

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title = "Small-Molecule Inhibitors of LRRK2",

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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author = "Hatcher, {John M.} and Choi, {Hwan Geun} and Alessi, {Dario R.} and Gray, {Nathanael S.}",

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T1 - Small-Molecule Inhibitors of LRRK2

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AU - Choi, Hwan Geun

AU - Alessi, Dario R.

AU - Gray, Nathanael S.

N1 - No funding info

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Parkinson’s disease

KW - Leucine-rich repeat kinase 2 (LRRK2)

KW - LRRK2 inhibitors

KW - Mutations

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DO - 10.1007/978-3-319-49969-7_13

M3 - Chapter (peer-reviewed)

C2 - 28353288

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Small-Molecule Inhibitors of LRRK2

Abstract

Publication series

Keywords

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Projects

Towards a Unifying Theory of Parkinson's Disease - Investigation of the Biochemical and Genetic Role of Rab GTPases (joint with German Centre for Neurodegenerative Diseases)

Cite this