Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis

Rebecca Banerjee, Anatoly A. Starkov, M. Flint Beal, Bobby Thomas

Research output: Contribution to journalReview article

173 Scopus citations

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with unknown etiology. It is marked by widespread neurodegeneration in the brain with profound loss of A9 midbrain dopaminergic neurons in substantia nigra pars compacta. Several theories of biochemical abnormalities have been linked to pathogenesis of PD of which mitochondrial dysfunction due to an impairment of mitochondrial complex I and subsequent oxidative stress seems to take the center stage in experimental models of PD and in postmortem tissues of sporadic forms of illness. Recent identification of specific gene mutations and their influence on mitochondrial functions has further reinforced the relevance of mitochondrial abnormalities in disease pathogenesis. In both sporadic and familial forms of PD abnormal mitochondrial paradigms associated with disease include impaired functioning of the mitochondrial electron transport chain, aging associated damage to mitochondrial DNA, impaired calcium buffering, and anomalies in mitochondrial morphology and dynamics. Here we provide an overview of specific mitochondrial functions affected in sporadic and familial PD that play a role in disease pathogenesis. We propose to utilize these gained insights to further streamline and focus the research to better understand mitochondria's role in disease development and exploit potential mitochondrial targets for therapeutic interventions in PD pathogenesis.

Original languageEnglish (US)
Pages (from-to)651-663
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1792
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • DJ-1
  • Electron transport chain
  • LRRK2
  • Mitochondrial DNA
  • Mitochondrial dysfunction
  • PINK1
  • Parkin
  • Permeability transition pore
  • α-synuclein

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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