Coenzyme a-acetylating enzymes in Alzheimer's disease: Possible cholinergic ‘compartment’ of pyruvate dehydrogenase

Perry, Elaine K.; Perry, Robert H.; Tomlinson, Bernard E.; Blessed, G.; Gibson, Peter H.

doi:10.1016/0304-3940(80)90220-7

Cited by 221 publications

(102 citation statements)

References 16 publications

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“…Assaying homogenates from the autopsied AD brain, Perry et al (23) revealed a decrease of pyruvate dehydrogenase (PDH) activity in the frontal, temporal, and parietal cortex, which was confirmed by several other studies (24 -26). Alphaketoglutarate dehydrogenase (KGDH) has been considered as a rate-limiting enzyme of the Krebs cycle and consists of 3 subunits, E1k, E2k and E3.…”

Section: Metabolic Enzyme Defects In Adsupporting

confidence: 53%

Mitochondrial Aβ A potential cause of metabolic dysfunction in Alzheimer's disease

Chen¹,

Yan²

2006

TBMB

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Deficits in mitochondrial function are a characteristic finding in Alzheimer's disease (AD), though the mechanism remains to be clarified. Recent studies revealed that amyloid β peptide (Aβ) gains access into mitochondrial matrix, which was much more pronounced in both AD brain and transgenic mutant APP mice than in normal controls. Aβ progressively accumulates in mitochondria and mediates mitochondrial toxicity. Interaction of mitochondrial Aβ with mitochondrial enzymes such as amyloid β binding alcohol dehydrogenase (ABAD) exaggerates mitochondrial stress by inhibiting the enzyme activity, releasing reactive oxygen species (ROS), and affecting glycolytic, Krebs cycle and/or the respiratory chain pathways through the accumulation of deleterious intermediate metabolites. The pathways proposed may play a key role in the pathogenesis of this devastating neurodegenerative disorder, Alzheimer's disease. iubmb Life, 58: 686‐694, 2006

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Section: Metabolic Enzyme Defects In Adsupporting

confidence: 53%

Mitochondrial Aβ A potential cause of metabolic dysfunction in Alzheimer's disease

Chen¹,

Yan²

2006

TBMB

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“…Earlier studies on autoptic human brain from AD patients have demonstrated decreases in pyruvate dehydrogenase complex activity [27], as well as α-ketoglutarate dehydrogenase [28,29]. However, the most consistent reported abnormality in mitochondrial enzyme activity is in cytochrome c oxidase [2][3][4][5][6]30].…”

Section: Mitochondrial Dysfunction In Admentioning

confidence: 99%

“…This was consistent with the results of binding studies in which Aβ(1-42), Aβ and Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) demonstrated dose-dependent saturable binding to ABAD. The C-terminal portion of Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) did not bind to ABAD, indicating that ABAD-Aβ interaction was not due to nonspecific interaction with aggregated or fibrillar material. This observation also suggested the possibility that Aβ might anchor, via its N-terminus, in ABAD thereby leaving the C-terminus free and allowing it to multimerize with additional Aβ.…”

Section: Targets Of Aβ In Mitochondriamentioning

confidence: 99%

Mitochondrial amyloid-beta peptide: Pathogenesis or late-phase development?

Yan

Xiong

Stern

2006

JAD

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Abstract. Mitochondrial and metabolic dysfunction have been linked to Alzheimer's disease for some time. Key questions regarding this association concern the nature and mechanisms of mitochondrial dysfunction, and whether such changes in metabolic properties are pathogenic or secondary, with respect to neuronal degeneration. In terms of mitochondria and Alzheimer's, altered function could reflect intrinsic properties of this organelle, potentially due to mutations in mitochondrial DNA, or extrinsic changes secondary to signal transduction mechanisms activated in the cytosol. This review presents data relevant to these questions, and considers the implication of recent findings demonstrating the presence of amyloid-β peptide in mitochondria, as well as intra-mitochondrial molecular targets with which it can interact. Regardless of the underlying mechanism(s), it is likely that mitochondrial dysfunction contributes to oxidant stress which is commonly observed in brains of patients with Alzheimer's and transgenic models of Alzheimer's-like pathology.

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“…Postmortem neurochemical studies on AD patients demonstrated a severe loss of cortical neurotransmitters, particularly in the cholinergic synthetic enzymes activities (16) and to a lesser extent in several other cortical neurotransmitters systems such as somatostatinergic (17), serotoninergic (18), and noradrenergic (1) neurotransmitters. In model experiments, it was found that Al(III) inhibits choline transport in rat brain (20), in rat synaptosomes from cortex and hippocampus (21), and in human erythrocytes (22) and reduced neural choline acetyltransferase activity in the rabbit (23).…”

Section: Reduction Of Neurotransmitter Activitymentioning

confidence: 99%