John Gordon Lindsay

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Microglial activation, oxidative stress, and dysfunctions in mitochondria, including the reduction of cytochrome oxidase activity, have been implicated in neurodegeneration. The current experiments tested the effects of reducing cytochrome oxidase activity on the ability of microglia to respond to inflammatory insults. Inhibition of cytochrome oxidase by(More)
Abnormalities in energy metabolism and oxidative stress accompany many neurodegenerative diseases, including progressive supranuclear palsy (PSP). Previously, we showed decreased activities of a mitochondrial enzyme complex, alpha-ketoglutarate dehydrogenase complex (KGDHC), and marked increases in tissue malondialdehyde levels in post-mortem superior(More)
To determine whether the reduction in brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease (AD) is associated with an abnormality in one of its three constituent enzyme subunits, we measured protein levels of alpha-ketoglutarate dehydrogenase (El), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3),(More)
The regional and cellular distributions of glucose transporter protein (GT) and pyruvate dehydrogenase (PDH) have been studied with an enhanced immunogold method. The results showed significant amounts of GT in neuropil within regions known to exhibit high demands for glucose whilst neuronal perikarya showed little immunostaining. In contrast PDH(More)
To test whether previously demonstrated reductions in the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC) in Alzheimer's disease (AD) brain also occur in morphologically normal AD tissues, we examined KGDHC in cultured skin fibroblasts from patients with familial AD (FAD). KGDHC activity was reduced by 44% in the FAD cells (p < 0.002) from(More)
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(More)
Alzheimer's disease (AD) is associated with a striking reduction in the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC). The deficiency occurs in brains from AD patients of undefined etiology, and in fibroblasts from both sporadic and familial AD cases. To further assess the nature of the abnormality of KGDHC in AD, KGDHC activities and(More)
Mammalian pyruvate dehydrogenase multienzyme complex (PDC) is a key metabolic assembly comprising a 60-meric pentagonal dodecahedral E2 (dihydrolipoamide acetyltransferase) core attached to which are 30 pyruvate decarboxylase E1 heterotetramers and 6 dihydrolipoamide dehydrogenase E3 homodimers at maximal occupancy. Stable E3 integration is mediated by an(More)
Mitochondrial dysfunction is a common feature of many neurodegenerative disorders. The metabolic encephalopathy caused by thiamine deficiency (TD) is a classic example in which an impairment of cerebral oxidative metabolism leads to selective cell death. In experimental TD in rodents, a reduction in the activity of the thiamine diphosphate-dependent,(More)
Primary biliary cirrhosis (PBC) is associated with serum antibodies that react with the dihydrolipoamide acetyltransferase component (E2) of the mitochondrial pyruvate dehydrogenase complex. We have sought the presence of E2 on the surface of human intrahepatic biliary epithelial cells (BEC). Cultured BECs from PBC but not normal liver were found to have E2(More)