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

NEUROBIOLOGY OF AGING

卷:35

Article

Dunn, Laura¹  Allen, George F. G.²  Mamais, Adamantios¹  Ling, Helen^1,6  Li, Abi⁶  Duberley, Kate E.⁷  Hargreaves, Iain P.⁷  Pope, Simon⁷  Holton, Janice L.⁶  Lees, Andrew¹  Heales, Simon J.^4,5,3  Bandopadhyay, Rina¹ 

[1] UCL Inst Neurol, Reta Lila Weston Labs, London, England

[2] Univ Dundee, MRC Prot Phosphorylat Unit, Dundee, Scotland

[3] UCL Inst Neurol, Dept Mol Neurosci, London, England

[4] Great Ormond St Hosp Sick Children, Dept Chem Pathol, London WC1N 3JH, England

[5] UCL Inst Child Hlth, Clin & Mol Genet Unit, London, England

[6] UCL Inst Neurol, Queen Sq Brain Bank, London, England

[7] Natl Hosp Neurol & Neurosurg, Neurometab Unit, London WC1N 3BG, England

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

DOI  :  10.1016/j.neurobiolaging.2013.11.001

来源: Elsevier

【 摘 要 】

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. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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