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Neurobiol Aging. 2014 May;35(5):1111-5. doi: 10.1016/j.neurobiolaging.2013.11.001. Epub 2013 Nov 9.

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease.

Author information

  • 1Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK. Electronic address: laura.dunn11@uclmail.net.
  • 2MRC Protein Phosphorylation Unit. University of Dundee, Dundee, UK.
  • 3Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
  • 4Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK; Queen Square Brain Bank, UCL Institute of Neurology, London, UK.
  • 5Queen Square Brain Bank, UCL Institute of Neurology, London, UK.
  • 6Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
  • 7Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
  • 8Chemical Pathology Department, Great Ormond Street Hospital, London, UK; Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Abstract

Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Glucose metabolism; NADPH; Neurodegeneration; Parkinson's disease; Pentose-phosphate pathway

PMID:
24300239
[PubMed - in process]
PMCID:
PMC3969149
Free PMC Article

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