Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain
Abstract
Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.
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There is a progressive age-related accumulation of oxidative damage to DNA in the human brain, and mitochondrial DNA is preferentially affected; increased 8-OHdG in mtDNA and nuclear DNA is demonstrated in the aging human brain and in Alzheimer's disease.
“It is demonstrated that there is a progressive age-related accumulation of oxidative damage to DNA in the human brain and that mtDNA is preferentially affected. The increased amount of 8-OHdG in mtDNA and nuclear DNA is demonstrated in the aging human brain and in AD [50,51,64].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [64]
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- Authors
- Mecocci, P., Beal, M. F., Cecchetti, R., Polidori, M. C., Cherubini, A., Chionne, F., Avellini, L., Romano, G., & Senin, U.
- Affiliations
- University of Perugia (IT)
- Harvard University (US)
- Venue
- Molecular and Chemical Neuropathology
- Published
- 1997-05
- Volume
- 31
- Issue
- 1
- Pages
- 53-64
- ISSN
- 1044-7393 (ISSN-L)
- OpenAlex
- W1974297683
- Cited by
- 215
- References
- 49
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 7 · 2012: 4
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular and Chemical Neuropathology (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- mitochondrial membrane fluidity, mitochondrial DNA oxidation, Alzheimer's disease, brain aging, oxidative stress, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, cerebellum, neurodegeneration
- MeSH terms
- Aged, Aging, Alzheimer Disease, Cerebral Cortex, DNA, Mitochondrial, Female, Humans, Intracellular Membranes, Male, Membrane Fluidity, Mitochondria, Viscosity, Oxidative Stress
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