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

Byoung Dae Lee, Joo Ho Shin, Jackalina Vankampen, Leonard Petrucelli, Andrew B. West, Han Seok Ko, Yun Il Lee, Kathleen A. Maguire-Zeiss, William J. Bowers, Howard J. Federoff, Valina L. Dawson, Ted M. Dawson

Research output: Contribution to journalArticlepeer-review

316 Scopus citations

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.

Original languageEnglish
Pages (from-to)998-1000
Number of pages3
JournalNature Medicine
Volume16
Issue number9
DOIs
StatePublished - Sep 2010

Bibliographical note

Funding Information:
We thank C. Burris and L. Lotta for packaging helper virus–free amplicons. C. Cook, K. Kehoe, J. Dunmore and C. Eckman provided technical support for some of the in vivo HSV studies. We also thank G. and K. Caldwell and S. Hamamichi for helpful discussions. This work was supported by grants from the US National Institutes of Health, P50NS38377, R01ES014470 (K.A.M.-Z.), R01-AG023593 (W.J.B.), R00-NS058111 (A.B.W.), NS36420 (H.J.F.) and Army Medical Research and Materiel Command, DAMD17-02-1-0695 (H.J.F.), the Mayo Foundation and the Michael J. Fox Foundation.

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