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PLATELET MITOCHONDRIAL-FUNCTION IN PARKINSONS-DISEASE

KRIGE, D; CARROLL, MT; COOPER, JM; MARSDEN, CD; SCHAPIRA, AHV; (1992) PLATELET MITOCHONDRIAL-FUNCTION IN PARKINSONS-DISEASE. ANN NEUROL , 32 (6) 782 - 788.

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Abstract

There is increasing evidence that defective function of the mitochondrial enzyme NADH CoQ reductase (complex I) is involved not only in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, but also in idiopathic Parkinson's disease (PD). Complex I deficiency has been identified in PD substantia nigra and appears to be disease-specific and selective for the substantia nigra within the central nervous system. We describe a method for preparation of an enriched mitochondrial fraction from 60 mL blood. Using this technique, we analyzed respiratory chain function in 25 patients with PD and 15 matched control subjects. We confirm a previous report of a specific complex I deficiency in PD platelet mitochondria. Although there was a statistically significant decrease in complex I activity in the PD group compared with the control group (p = 0.005), the defect was mild (16%); it was not possible to distinguish PD from control values on an individual basis. This deficiency is not detectable in platelet whole-cell homogenates, presumably reflecting the relative insensitivity of this preparation and the limited decrease in complex I activity in PD. The presence of a mild complex I defect in platelets together with a more severe defect in substantia nigra suggests either that the pharmacological characteristics shared by these two tissues render them susceptible to a particular toxin or toxins, or that the defect is widely distributed and other biochemical events enhance the deficiency in substantia nigra. Evidence for a complex I defect in platelet mitochondria from patients with PD supports the proposition that this biochemical deficiency may have some role in the cause of dopaminergic cell death in this disorder.

Type: Article
Title: PLATELET MITOCHONDRIAL-FUNCTION IN PARKINSONS-DISEASE
Keywords: COMPLEX-I DEFICIENCY, BRAIN MITOCHONDRIA, HUNTINGTONS-DISEASE, SUBSTANTIA NIGRA, NADH, DEFECT, N-METHYL-4-PHENYLPYRIDINE, OXIDOREDUCTASE, NEUROTOXIN, METABOLITE
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/127534
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