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Abnormalities of mitochondrial enzymes in Alzheimer disease
Abstract
Abundant evidence, including critical information gathered by Prof. Siegfried Hoyer and his colleagues, indicates that abnormalities of cerebral metabolism are common in neurodegenerative diseases, including Alzheimer's Disease (AD). Alterations in mitochondrial enzymes likely underlie these deficits. Replicable reductions in AD brain occur in the pyruvate dehydrogenase complex (the link of glycolysis to the Kreb's cycle), the alpha-ketoglutarate dehydrogenase complex (KGDHC; the link of Kreb's cycle to glutamate metabolism) and cytochrome oxidase (the link of the Kreb's cycle to oxygen utilization). Available evidence suggests that deficiencies in KGDHC may be genetic in some cases, whereas evidence that the other two enzyme systems have a genetic component is lacking. Additional results indicate that the reductions can also be secondary to other causes including oxidative stress. A variety of data suggest that the mitochondrial insufficiencies contribute significantly to the pathophysiology of AD.
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“Relative to control brains, in AD brains several mitochondrial enzymes have reduced Vmax activities. Examples include two dehydrogenase enzymes, pyruvate dehydrogenase and ketoglutarate dehydrogenase [124].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [124]
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1 retracted
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RetractedOxidative stress hypothesis in Alzheimer’s disease
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“Deficiency of COX activity in platelets has been reported (Parker et al., 1990) and disputed (VanZuylen et al., 1992).”
BackgroundBrain cytochrome oxidase in Alzheimer's disease
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Metadata
- Authors
- Gibson, G. E., Sheu, K.-F. R., & Blass, J. P.
- Affiliations
- Cornell University (US)
- ORCID
- Gibson, G. E.
- Venue
- Journal of Neural Transmission
- Published
- 1998-11-04
- Volume
- 105
- Issue
- 8-9
- Pages
- 855-870
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W1989462226
- Cited by
- 345
- References
- 59
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 14 · 2022: 14 · 2021: 12 · 2020: 20 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 23 · 2015: 19 · 2014: 7 · 2013: 14 · 2012: 12
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r35ag009014-07)
- National Institute on Aging (AG11921, AG 09014, R01AG014600, R01AG011921, AG-14600)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- Alzheimer's disease, mitochondrial enzymes, pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, cytochrome c oxidase, brain metabolism, neurodegeneration, oxidative stress, TCA cycle, glutamate metabolism, genetic deficiency
- MeSH terms
- Alzheimer Disease, Electron Transport Complex IV, Humans, Ketoglutarate Dehydrogenase Complex, Mitochondria, Pyruvate Dehydrogenase Complex, Oxidative Stress
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