Cell death pathways in Parkinson's disease: role of mitochondria

Antioxid Redox Signal. 2009 Sep;11(9):2135-49. doi: 10.1089/ars.2009.2624.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease and is characterized pathologically by selective loss of nigrostriatal dopaminergic neurons and the formation of Lewy bodies. Although in the majority of cases the cause of PD is unknown, mitochondrial dysfunction, environmental toxins, oxidative stress, and abnormal protein accumulation may all be involved in disease pathogenesis. The discovery of genes causing rare familial forms of PD (including alpha-synuclein, parkin, DJ-1, PINK1, and LRRK2) has shed light on our understanding of the molecular mechanisms of the development of the disease. Further studies from transgenic or toxin-induced experimental models have also provided insights into the etiology of human disease. Recently, accumulating evidence has suggested that mitochondrial dysfunction is one of the key players in molecular cell death pathways of PD. In this review, we provide an overview of the role of mitochondria in the pathogenesis of both sporadic and familial forms of PD. We also discuss the links between different pathways and highlight novel therapeutic opportunities which target mitochondria.

Publication types

  • Review

MeSH terms

  • Cell Death*
  • Cell Nucleus / metabolism
  • DNA / genetics
  • Humans
  • Mitochondria / metabolism*
  • Oxidative Stress
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*

Substances

  • DNA