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

Nat Med. 2010 Sep;16(9):998-1000. doi: 10.1038/nm.2199. Epub 2010 Aug 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation
  • Neurons / physiology
  • Parkinson Disease / genetics
  • Parkinson Disease / prevention & control*
  • 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

Substances

  • Protein Kinase Inhibitors
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases