Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2

Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson’s disease. We employed a novel, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces...

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Autores principales: Deng, Xianming, Dzamko, Nicolas, Prescott, Alan, Davies, Paul, Liu, Qingsong, Yang, Qingkai, Lee, Jiing-Dwan, Patricelli, Matthew P., Nomanbhoy, Tyzoon K., Alessi, Dario R., Gray, Nathanael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287420/
https://www.ncbi.nlm.nih.gov/pubmed/21378983
http://dx.doi.org/10.1038/nchembio.538
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author Deng, Xianming
Dzamko, Nicolas
Prescott, Alan
Davies, Paul
Liu, Qingsong
Yang, Qingkai
Lee, Jiing-Dwan
Patricelli, Matthew P.
Nomanbhoy, Tyzoon K.
Alessi, Dario R.
Gray, Nathanael S.
author_facet Deng, Xianming
Dzamko, Nicolas
Prescott, Alan
Davies, Paul
Liu, Qingsong
Yang, Qingkai
Lee, Jiing-Dwan
Patricelli, Matthew P.
Nomanbhoy, Tyzoon K.
Alessi, Dario R.
Gray, Nathanael S.
author_sort Deng, Xianming
collection PubMed
description Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson’s disease. We employed a novel, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910/Ser935 and accumulation of LRRK2 within aggregate structures. LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson’s disease.
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spelling pubmed-32874202012-02-27 Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2 Deng, Xianming Dzamko, Nicolas Prescott, Alan Davies, Paul Liu, Qingsong Yang, Qingkai Lee, Jiing-Dwan Patricelli, Matthew P. Nomanbhoy, Tyzoon K. Alessi, Dario R. Gray, Nathanael S. Nat Chem Biol Article Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson’s disease. We employed a novel, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910/Ser935 and accumulation of LRRK2 within aggregate structures. LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson’s disease. 2011-03-06 2011-04 /pmc/articles/PMC3287420/ /pubmed/21378983 http://dx.doi.org/10.1038/nchembio.538 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Deng, Xianming
Dzamko, Nicolas
Prescott, Alan
Davies, Paul
Liu, Qingsong
Yang, Qingkai
Lee, Jiing-Dwan
Patricelli, Matthew P.
Nomanbhoy, Tyzoon K.
Alessi, Dario R.
Gray, Nathanael S.
Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title_full Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title_fullStr Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title_full_unstemmed Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title_short Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2
title_sort characterization of a selective inhibitor of the parkinson’s disease kinase lrrk2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287420/
https://www.ncbi.nlm.nih.gov/pubmed/21378983
http://dx.doi.org/10.1038/nchembio.538
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