The genetics of Parkinson disease

J Geriatr Psychiatry Neurol. 2010 Dec;23(4):228-42. doi: 10.1177/0891988710383572. Epub 2010 Oct 11.

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disorder. In most instances, PD is thought to result from a complex interaction between multiple genetic and environmental factors, though rare monogenic forms of the disease do exist. Mutations in 6 genes (SNCA, LRRK2, PRKN, DJ1, PINK1, and ATP13A2) have conclusively been shown to cause familial parkinsonism. In addition, common variation in 3 genes (MAPT, LRRK2, and SNCA) and loss-of-function mutations in GBA have been well-validated as susceptibility factors for PD. The function of these genes and their contribution to PD pathogenesis remain to be fully elucidated. The prevalence, incidence, clinical manifestations, and genetic components of PD are discussed in this review.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / psychology
  • Animals
  • Calcium-Binding Proteins
  • Carrier Proteins / genetics*
  • Exons
  • Gene Expression
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Glucosylceramidase / genetics
  • Humans
  • Incidence
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation
  • Parkinson Disease / diagnosis
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Proton-Translocating ATPases / genetics
  • Repressor Proteins
  • Risk Factors
  • Ubiquitin-Protein Ligases / classification
  • Ubiquitin-Protein Ligases / genetics*
  • alpha-Synuclein / genetics*
  • tau Proteins / genetics

Substances

  • ATP13A2 protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • EFCAB6 protein, human
  • MAPT protein, human
  • Repressor Proteins
  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • Glucosylceramidase
  • Proton-Translocating ATPases