Impact of recent genetic findings in Parkinson's disease

Curr Opin Neurol. 2007 Aug;20(4):453-64. doi: 10.1097/WCO.0b013e3281e6692b.


Purpose of review: Parkinson's disease is the second most common age-related neurodegenerative disorder and is characterized clinically by classical parkinsonism and pathologically by selective loss of dopaminergic neurons in the substantia nigra and Lewy bodies. Although for most classical parkinsonism the etiology is unknown, a clear genetic component has been determined in a minority. Mutations in five causative genes combined [alpha-Synuclein (SNCA), Parkin, PTEN-induced kinase 1 (PINK1), DJ-1, Leucine-rich repeat kinase 2 (LRRK2)] account for 2-3% of all cases with classical parkinsonism, often clinically indistinguishable from idiopathic Parkinson's disease.

Recent findings: The functional role of PINK1 and LRRK2 as kinases has been clearly established. Further, mutations in the ATP13A2 gene have been linked to Kufor-Rakeb syndrome (PARK9), a form of atypical parkinsonism. ATP13A2 encodes a lysosomal ATPase and shows elevated expression levels in the brains of sporadic patients, suggesting a potential role in the more common idiopathic Parkinson's disease. Finally, first promising pilot studies have been performed to identify differentially expressed genes and proteins as biomarkers for parkinsonism.

Summary: The identification of single genes and their functional characterization has enhanced our understanding of the pathogenesis of parkinsonism, has led to improvement of diagnostic tools for genetic parkinsonism, and allows for the purposeful consideration of novel therapeutic targets.

Publication types

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

MeSH terms

  • Diagnosis, Differential
  • Genetic Predisposition to Disease
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Parkinson Disease / classification
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy
  • Protein Deglycase DJ-1
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism


  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • alpha-Synuclein
  • 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
  • PARK7 protein, human
  • Protein Deglycase DJ-1