Zeroing in on LRRK2-linked pathogenic mechanisms in Parkinson's disease

Biochim Biophys Acta. 2009 Jul;1792(7):625-33. doi: 10.1016/j.bbadis.2008.09.015. Epub 2008 Oct 10.

Abstract

The frequency and potency of mutations in the LRRK2 gene redefine the role of genetic susceptibility in Parkinson's disease. Dominant missense mutations that fulfill initial criteria for potential gain of function mechanisms coupled with enzymatic activity likely amenable to small molecule inhibition position LRRK2 as a promising therapeutic target. Herein, key observations from the clinic to the test tube are highlighted together with points of contention and outstanding critical issues. Resolution of the critical issues will expedite the development of therapies that exploit LRRK2 activity for neuroprotection strategies.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / toxicity

Substances

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