LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson's disease

Neurochem Res. 2007 Oct;32(10):1700-8. doi: 10.1007/s11064-007-9324-y. Epub 2007 Apr 18.

Abstract

The identification of mutations in the leucine-rich repeat kinase 2 (LRRK2) gene as a cause of autosomal dominant Parkinson's disease (PD) was a major step forward in the genetic dissection of this disorder. However, what makes LRRK2 unique among the known PD-causing genes is that a low-penetrance mutation, Gly2019Ser, is a frequent determinant not only of familial, but also of sporadic PD in several populations from South Europe, North Africa and Middle East. Moreover, a different polymorphic variant, Gly2385Arg, is a frequent risk factor for PD among Chinese and Japanese populations. Currently, the Gly2019Ser and Gly2385Arg variants represent the most relevant PD-causing mutation and risk allele, respectively, linking the etiology of the familial and the sporadic forms of this disease. Understanding how the dysfunction of LRRK2 protein leads to neurodegeneration might provide crucial insights for unraveling the molecular mechanisms of PD and for developing disease-modifying therapies.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Asia / epidemiology
  • Glycine / genetics
  • Glycine / physiology
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation / physiology*
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / genetics*
  • Penetrance*
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk
  • Serine / genetics
  • Serine / physiology

Substances

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