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The development of inhibitors of leucine-rich repeat kinase 2 (LRRK2) as a therapeutic strategy for Parkinson's disease: the current state of play.

Azeggagh, S; Berwick, DC (2022) The development of inhibitors of leucine-rich repeat kinase 2 (LRRK2) as a therapeutic strategy for Parkinson's disease: the current state of play. Br J Pharmacol, 179 (8). pp. 1478-1495. ISSN 1476-5381 https://doi.org/10.1111/bph.15575
SGUL Authors: Berwick, Daniel Charles

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Abstract

Current therapeutic approaches for Parkinson's disease (PD) are based around treatments that alleviate symptoms but do not slow or prevent disease progression. As such, alternative strategies are needed. A promising approach is the use of molecules that reduce the function of leucine-rich repeat kinase (LRRK2). Gain-of-function mutations in LRRK2 account for a notable proportion of familial Parkinson's disease cases, and significantly, elevated LRRK2 kinase activity is reported in idiopathic Parkinson's disease. Here, we describe progress in finding therapeutically effective LRRK2 inhibitors, summarising studies that range from in vitro experiments to clinical trials. LRRK2 is a complex protein with two enzymatic activities and a myriad of functions. This creates opportunities for a rich variety of strategies and also increases the risk of unintended consequences. We comment on the strength and limitations of the different approaches and conclude that with two molecules under clinical trial and a diversity of alternative options in the pipeline, there is cause for optimism.

Item Type: Article
Additional Information: © 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Kinase inhibitor, LRRK2, Neurodegeneration, Parkinson's disease, Kinase inhibitor, LRRK2, Neurodegeneration, Parkinson's disease, 1115 Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Br J Pharmacol
ISSN: 1476-5381
Language: eng
Dates:
DateEvent
15 March 2022Published
22 June 2021Published Online
21 May 2021Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDOpen UniversityUNSPECIFIED
PubMed ID: 34050929
Web of Science ID: WOS:000665556200001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/113335
Publisher's version: https://doi.org/10.1111/bph.15575

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