gw-5074 and indirubin-3--monoxime

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.. A paper suggesting that inhibitors of Gly2019Ser mutant may be useful in the treatment of Parkinson's disease associated with this mutant is evaluated.. 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.. 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.

Topics: Animals; Antiparkinson Agents; Cell Culture Techniques; Cell Death; Corpus Striatum; Genetic Vectors; Indoles; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mice; Mutation; Nerve Degeneration; Oximes; Parkinson Disease; Phenols; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Simplexvirus; Tyrosine 3-Monooxygenase