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

Laura Dunn (Lead / Corresponding author), George F. G. Allen, Adamantios Mamais, Helen Ling, Abi Li, Kate E. Duberley, Iain P. Hargreaves, Simon Pope, Janice L. Holton, Andrew Lees, Simon J. Heales, Rina Bandopadhyay

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    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.
    Original languageEnglish
    Pages (from-to)1111-1115
    Number of pages5
    JournalNeurobiology of Aging
    Volume35
    Issue number5
    DOIs
    Publication statusPublished - May 2014

    Keywords

    • Aged
    • Aged, 80 and over
    • Animals
    • Antioxidants
    • Cell Death
    • Cerebellum
    • Dopaminergic Neurons
    • Female
    • Glucose
    • Glucosephosphate Dehydrogenase
    • Humans
    • Male
    • NADP
    • Neurons
    • Parkinson Disease
    • Pentose Phosphate Pathway
    • Phosphogluconate Dehydrogenase
    • Putamen

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  • Cite this

    Dunn, L., Allen, G. F. G., Mamais, A., Ling, H., Li, A., Duberley, K. E., Hargreaves, I. P., Pope, S., Holton, J. L., Lees, A., Heales, S. J., & Bandopadhyay, R. (2014). Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease. Neurobiology of Aging, 35(5), 1111-1115. https://doi.org/10.1016/j.neurobiolaging.2013.11.001