TY  - JOUR
AV  - public
Y1  - 2014/11//
VL  - 35
SP  - 1111
EP  - 1115
TI  - Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease.
IS  - 5
N1  - ?© 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which permits
non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
UR  - http://dx.doi.org/10.1016/j.neurobiolaging.2013.11.001
N2  - 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.
ID  - discovery1416406
A1  - Dunn, L
A1  - Allen, GF
A1  - Mamais, A
A1  - Ling, H
A1  - Li, A
A1  - Duberley, KE
A1  - Hargreaves, IP
A1  - Pope, S
A1  - Holton, JL
A1  - Lees, A
A1  - Heales, SJ
A1  - Bandopadhyay, R
KW  - Glucose metabolism
KW  -  NADPH
KW  -  Neurodegeneration
KW  -  Parkinson's disease
KW  -  Pentose-phosphate pathway
JF  - Neurobiol Aging
ER  -