Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease.
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.
Lee
Byoung Dae
BD
Neuroregeneration Program, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Shin
Joo-Ho
JH
VanKampen
Jackalina
J
Petrucelli
Leonard
L
West
Andrew B
AB
Ko
Han Seok
HS
Lee
Yun-Il
YI
Maguire-Zeiss
Kathleen A
KA
Bowers
William J
WJ
Federoff
Howard J
HJ
Dawson
Valina L
VL
Dawson
Ted M
TM
D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000517:prevention & control*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics / Q000633:toxicity
D047428:Protein Kinase Inhibitors; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases