Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

• Published in: Nature medicine Vol. 16; no. 9; pp. 998 - 1000
• Main Authors: Dawson, Valina L, Dawson, Ted M, Lee, Byoung Dae, Shin, Joo-Ho, VanKampen, Jackalina, Petrucelli, Leonard, West, Andrew B, Ko, Han Seok, Lee, Yun-Il, Maguire-Zeiss, Kathleen A, Bowers, William J, Federoff, Howard J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2010; Nature Publishing Group
• Subjects: 631/154/436; 692/699/375/365/1718; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Care and treatment; Disease prevention; Genetic aspects; Health aspects; Humans; Infectious Diseases; Inhibitor drugs; Inhibitors; Kinases; Leucine; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Metabolic Diseases; Molecular Medicine; Mutation; Neurons; Neurons - physiology; Neurosciences; Neurotoxic agents; Parkinson Disease - genetics; Parkinson Disease - prevention & control; Parkinson's disease; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - drug effects; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - toxicity
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.2199

Leucine-rich repeat kinase-2 (LRRK2) mutations are a common cause of Parkinson's disease. Here we identify inhibitors of LRRK2 kinase that are protective in in vitro and in vivo models of LRRK2-induced neurodegeneration. These results establish that LRRK2-induced degeneration of neurons in vivo is kinase dependent and that LRRK2 kinase inhibition provides a potential new neuroprotective paradigm for the treatment of Parkinson's disease.