Journal
JOURNAL OF NEUROSCIENCE METHODS
Volume 214, Issue 1, Pages 62-68Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2012.12.015
Keywords
LRRK2; Kinase domain; Activation segment; Conformation; Antibody; Immunoprecipitation
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Funding
- NGFN-Plus [FKZ: 01GS08140, 12]
- HelMA [FKZ: HA-215, topic 3 WP11]
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. LRRK2 kinase activity is required for toxicity in neuronal cell cultures suggesting that selective kinase inhibitors may prevent neurodegeneration in patients. Directly monitoring LRRK2 activity in cells would be advantageous for the development of small molecule LRRK2 inhibitors. Here, we demonstrate that a monoclonal anti-LRRK2 antibody directed against the activation segment binds less efficiently to native LRRK2 protein in the presence of ATP-competitive LRRK2 inhibitors. Since kinase inhibitors prevent autophosphorylation and refolding of the activation segment, we hypothesize that the antibody preferentially binds to the active conformation of LRRK2 under native conditions. (c) 2013 Elsevier B.V. All rights reserved.
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