Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism

Annadurai Anandhan, Maria S. Jacome, Shulei Lei, Pablo Hernandez-Franco, Aglaia Pappa, Mihalis I. Panayiotidis, Robert Powers, Rodrigo Franco

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism.

Original languageEnglish (US)
Pages (from-to)12-30
Number of pages19
JournalBrain Research Bulletin
Volume133
DOIs
StatePublished - Jul 2017

Keywords

  • Bioenergetics
  • Glucose
  • Glycolysis
  • Mitochondria
  • Neurodegeneration
  • Oxidative stress
  • TCA cycle

ASJC Scopus subject areas

  • Neuroscience(all)

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