Cited by 275Mitochondrial Function and PathologyAlzheimer's disease research and treatmentsCoenzyme Q10 studies and effects

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Cybrids in Alzheimer's disease: A cellular model of the disease?

Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Maguire, D. J., Maguire, R. S., Bennett, J. P., Davis, Robert E., Parker, W. D.·1997·Neurology

DOI 10.1212/wnl.49.4.918

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Abstract

The mitochondrial electron transport chain enzyme cytochrome c oxidase (COX) is defective in patients with sporadic Alzheimer's disease (AD). This defect arises from the mutation of mitochondrial DNA (mtDNA). To develop a tissue culture system that would express this genetically derived bioenergetic lesion and permit characterization of its functional consequences, we depleted Ntera2/D1 (NT2) teratocarcinoma cells of endogenous mtDNA and repopulated them with platelet mtDNA from AD patients. Cytochrome c oxidase activity was depressed in the resulting AD cytoplasmic hybrids (cybrids) compared with cybrids prepared with mtDNA from non-AD controls. Reactive oxygen species (ROS) production and free radical scavenging enzyme activities were significantly elevated in AD cybrids. A COX defect in NT2 AD cybrid lines indicates that AD patients possess mtDNA COX gene mutations that are sufficient for determining this biochemical lesion. Expression of unique functional characteristics (increased ROS production and free radical scavenging enzyme activities) relevant to neurodegeneration demonstrates the utility of these cells in defining AD pathophysiology at a cellular level. This in vitro tissue culture model of AD may prove useful in drug screening.

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Authors: Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Maguire, D. J., Maguire, R. S., Bennett, J. P., Davis, R. E., & Parker, W. D.
Affiliations: Griffith University (AU)
ORCID: Swerdlow, R. H.
Cassarino, D. S.
Bennett, J. P.
Davis, Robert E.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1997-10
Volume: 49
Issue: 4
Pages: 918-925
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.49.4.918
OpenAlex: W4320578147
Cited by: 272
References: 18
Citations by year: 2026: 2 · 2025: 5 · 2024: 4 · 2023: 11 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 12 · 2012: 11
FWCI: 4.71
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5t32ns007199-15)
National Institute of Neurological Disorders and Stroke (NS-07199, NS34325)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Keywords: Alzheimer's disease, cybrids, cytochrome c oxidase, mitochondrial DNA mutations, mitochondrial electron transport chain, reactive oxygen species, free radical scavenging enzymes, neurodegeneration, drug screening
MeSH terms: Alzheimer Disease, Brain, Electron Transport Complex IV, Cytoplasm, DNA, Mitochondrial, Genetic Techniques, Humans, Hybridization, Genetic, Mutation, Reference Values, Tumor Cells, Cultured, Reactive Oxygen Species, Gene Transfer Techniques, Teratocarcinoma

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Cybrids in Alzheimer's disease: A cellular model of the disease?

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