The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

Nat Rev Neurosci. 2010 Dec;11(12):791-7. doi: 10.1038/nrn2935. Epub 2010 Nov 19.


Parkinson's disease, like many common age-related conditions, is now recognized to have a substantial genetic component. Here, I discuss how mutations in a large complex gene--leucine-rich repeat kinase 2 (LRRK2)--affect protein function, and I review recent evidence that LRRK2 mutations affect pathways that involve other proteins that have been implicated in Parkinson's disease, specifically α-synuclein and tau. These concepts can be used to understand disease processes and to develop therapeutic opportunities for the treatment of Parkinson's disease.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Dopamine / metabolism
  • Genetic Predisposition to Disease* / genetics
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Models, Biological
  • Mutation / genetics*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Risk Factors
  • alpha-Synuclein / metabolism
  • tau Proteins / metabolism


  • alpha-Synuclein
  • tau Proteins
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Dopamine