Understanding the molecular causes of Parkinson's disease

Trends Mol Med. 2006 Nov;12(11):521-8. doi: 10.1016/j.molmed.2006.09.007. Epub 2006 Oct 5.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that is both common and incurable. The majority of cases are sporadic and of unknown origin but several genes have been identified that, when mutated, give rise to rare, familial forms of the disease. The principal genes that have been shown to cause PD are alpha-synuclein (SNCA), parkin, leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1) and DJ-1. Here, we discuss what has been learnt from the study of these genes and what has been elucidated of the molecular pathways that lead to cell degeneration. Of importance is what these molecular events and pathways tell scientists of the common sporadic form of PD. Although complete knowledge of these genes' functions remains elusive, recent work implicates abnormal protein accumulation, protein phosphorylation, mitochondrial dysfunction and oxidative stress as common pathways to PD pathogenesis.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Cell Death
  • Chromosome Aberrations
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Middle Aged
  • Models, Biological
  • Mutation
  • Oxidative Stress
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Serine-Threonine Kinases / physiology
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / metabolism*
  • alpha-Synuclein / physiology

Substances

  • 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