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

ABSTRACT: 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.

SUBMITTER: Lee BD

PROVIDER: S-EPMC2935926 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Lee Byoung Dae BD 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

Nature medicine 20100822 9

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. ...[more]

PMID: 20729864

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