Molecular pathogenesis of Parkinson's disease: update

J Neurol Neurosurg Psychiatry. 2012 Apr;83(4):430-6. doi: 10.1136/jnnp-2011-301205. Epub 2011 Dec 3.

Abstract

Parkinson disease (PD) is a neurodegenerative disease characterised by progressive disturbances in motor, autonomic and psychiatric functions. Much has been learnt since the disease entity was established in 1817. Although there are well established treatments that can alleviate the symptoms of PD, a pressing need exists to improve our understanding of the pathogenesis to enable development of disease modifying treatments. Ten responsible genes for PD have been identified and recent progress in molecular research on the protein functions of the genes provides new insights into the pathogenesis of hereditary as well as sporadic PD. Also, genome wide association studies, a powerful approach to identify weak effects of common genetic variants in common diseases, have identified a number of new possible PD associated genes, including PD genes previously detected. However, there is still much to learn about the interactions of the gene products, and important insights may come from chemical and genetic screens. In this review, an overview is provided of the molecular pathogenesis and genetics of PD, focusing particularly on the functions of the PD related gene products with marked research progress.

Publication types

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

MeSH terms

  • Endoplasmic Reticulum-Associated Degradation / genetics
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Group VI Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / metabolism
  • 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 / genetics*
  • Protein Deglycase DJ-1
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism
  • Ubiquitin / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / genetics
  • tau Proteins / metabolism

Substances

  • ATP13A2 protein, human
  • F-Box Proteins
  • FBXO7 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Oncogene Proteins
  • Ubiquitin
  • 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
  • Group VI Phospholipases A2
  • PLA2G6 protein, human
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Proton-Translocating ATPases