title: Screening for chemical modulators for LRRK2.
abstract: After the discovery of leucine-rich repeat kinase 2 (LRRK2) as a risk factor for sporadic Parkinson's disease (PD) and mutations in LRRK2 as a cause of some forms of familial PD, there has been substantial interest in finding chemical modulators of LRRK2 function. Most of the pathogenic mutations in LRRK2 are within the enzymatic cores of the protein; therefore, many screens have focused on finding chemical modulators of this enzymatic activity. There are alternative screening approaches that could be taken to investigate compounds that modulate LRRK2 cellular functions. These screens are more often phenotypic screens. The preparation for a screen has to be rigorous and enable high-throughput accurate assessment of a compound's activity. The pipeline to beginning a drug screen and some LRRK2 inhibitor and phenotypic screens will be discussed.
authors.affiliation: SITraN, Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, U.K.
authors.forename: Heather
authors.initials: H
authors.lastname: Mortiboys
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: high-throughput screening; leucine-rich repeat kinase; mitochondria; phenotypic screening