Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2): Parkinson's disease and beyond

BMB Rep. 2015 May;48(5):243-8. doi: 10.5483/bmbrep.2015.48.5.032.

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing evidence is suggesting that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and the carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to the yet unknown diverse functions of LRRK2. Here, we reviewed current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discussed the possibility of targeting LRRK2 in such diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / physiopathology
  • Humans
  • Inflammatory Bowel Diseases / physiopathology
  • Leprosy / physiopathology
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Neoplasms / physiopathology
  • Parkinson Disease / physiopathology*
  • Protein Serine-Threonine Kinases / physiology*

Substances

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