title: A new approach to Parkinson's disease: inhibition of leucine-rich repeat kinase-2.
abstract: BACKGROUND
  Genetic studies have shown that mutations in several genes may be linked to Parkinson's disease including leucine-rich repeat kinase-2 (LRRK2). The most common of the LRRK2 mutants is the Gly2019Ser mutant.
  
  
  OBJECTIVE
  A paper suggesting that inhibitors of Gly2019Ser mutant may be useful in the treatment of Parkinson's disease associated with this mutant is evaluated.
  
  
  RESULTS
  Overexpression of the wild-type LRRK2 or the Gly2019Ser LRRK2 mutant type produced cortical neuron injury in cell culture, and the mutant also caused cell death; this was reduced by GW5074. Administered intraperitoneally to mice, GW5074 prevented the loss of neurons induced by the Gly2019Ser LRRK2 mutant.
  
  
  CONCLUSIONS
  Selective Gly2019Ser LRRK2 mutant inhibitors may have potential in the treatment of Parkinsonism associated with mutations of this gene and GW5074 is a lead compound for this.
authors.affiliation: Queensland University of Technology, Discipline of Medical Sciences, Faculty of Science and Technology, Brisbane, Australia. sheila.doggrell@qut.edu.au
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Doggrell
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D009154:Mutation; D009410:Nerve Degeneration / Q000188:drug therapy*; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D018139:Simplexvirus / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D007211:Indoles; D010091:Oximes; D010636:Phenols; C474021:indirubin-3'-monoxime; D014446:Tyrosine 3-Monooxygenase; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone