The DOI matches its Crossref record; 58 of the 59 references it cites were found in a registry or an index.
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
Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4526 · Cited by 341
RetractedOxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604
Cytochrome oxidase deficiency in Alzheimer’s disease
Parker, W. D., Filley, C. M., & Parks, J. K. (1990) · Neurology · doi:10.1212/wnl.40.8.1302 · Cited by 598 · cited 2×
“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
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537
Bolaños, J. P., Almeida, Á., Stewart, V. C., Peuchen, S., Land, J. M., Clark, J. B., & Heales, S. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68062227.x · Cited by 519
Goodman, Y., & Mattson, M. P. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1107 · Cited by 449
Cruts, M., van Duijn, C. M., Backhovens, H., den Broeck, M. V., Wehnert, A., Serneels, S., Sherrington, R., Hutton, M., Hardy, J., George‐Hyslop, P. S., et al. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.1.43 · Cited by 432
Gibson, G. E., Sheu, K. ‐. R., Blass, J. P., Baker, A., Carlson, K., Harding, B. N., & Perrino, P. (1988) · Archives of Neurology · doi:10.1001/archneur.1988.00520320022009 · Cited by 425
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1 of the 59 references couldn’t be matched to a known paper.
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Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357
Reddy, P. H., & Beal, M. F. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.002 · Cited by 975
Mitochondrial Dysfunction in Neurodegenerative Diseases
Johri, A., & Beal, M. F. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.192138 · Cited by 806
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723
Alzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626
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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