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Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson's disease.

Gibson, GE; Kingsbury, AE; Xu, H; Lindsay, JG; Daniel, S; Foster, OJF; Lees, AJ; (2003) Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson's disease. Neurochem Int , 43 (2) pp. 129-135.

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Abstract

Parkinson's disease (PD) is associated with mitochondrial dysfunction, specifically a deficiency of complex I of the electron transport chain. Most, although not all, studies indicate that this deficiency is limited to brain regions with neurodegeneration. The current studies tested for deficiencies in other mitochondrial components in PD brain in a neuropathologically unaffected region where the abnormality cannot be attributed to secondary effects of neurodegeneration. The activity of a key (and arguably rate-limiting) tricarboxylic acid cycle enzyme, the alpha-ketoglutarate dehydrogenase complex (KGDHC), was measured in the cerebellum of patients with PD. Activity in 19 PD brains was 50.5% of that in 18 controls matched for age, sex, post-mortem interval, and method of preservation (P<0.0019). The protein subunits of KGDHC were present in normal amounts in PD brains, indicating a relatively discrete abnormality in the enzyme. The activities of another mitochondrial enzyme, glutamate dehydrogenase (GDH), were normal in PD brains. These results demonstrate that specific reductions in KGDHC occur even in pathologically unaffected areas in PD, where the decline is unlikely to be a non-specific result of neurodegeneration. Reductions in the activity of this enzyme, if widespread in the brain, may predispose vulnerable regions to further damage.

Type: Article
Title: Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson's disease.
Location: England
Keywords: Adolescent, Adult, Brain, Cadaver, Cause of Death, Child, Citric Acid Cycle, Female, Glutamate Dehydrogenase, Humans, Ketoglutarate Dehydrogenase Complex, Male, Middle Aged, Multienzyme Complexes, NADH, NADPH Oxidoreductases, Parkinsonian Disorders, Reference Values
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/116013
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