β‐Amyloid fragment 25–35 selectively decreases complex IV activity in isolated mitochondria
Open accessAbstract
Defects in mitochondrial oxidative metabolism, in particular decreased activity of cytochrome c oxidase, have been demonstrated in Alzheimer's disease, and after the expression of the amyloid precursor protein (APP) in cultured cells, suggesting that mitochondria might be involved in β‐amyloid toxicity. Recent evidence suggests that the proteolysis of APP to generate β‐amyloid is at least in part intracellular, preceding the deposition of extracellular fibrils. We have therefore investigated the effect of incubation of isolated rat brain mitochondria with the β‐amyloid fragment 25–35 (100 μM) on the activities of the mitochondrial respiratory chain complexes I, II–III, IV (cytochrome c oxidase) and citrate synthase. The peptide caused a rapid, dose‐dependent decrease in the activity of complex IV, while it had no effect on the activities on any of the other enzymes tested. The reverse sequence peptide (35–25) had no effect on any of the activities measured. We conclude that inhibition of mitochondrial complex IV might be a contributing factor to the pathogenesis of Alzheimer's disease.
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Aβ increases reactive species in neurons via multiple mechanisms, including direct Aβ-induced RS production, elevated NADPH oxidase activity, interaction with mitochondria-associated Aβ alcohol dehydrogenase, inhibition of cytochrome oxidase (respiratory complex IV), and leakage of electrons from the mitochondrial electron transport chain.
“Aβ is reported to increase RS in neurons via multiple mechanisms, including direct Aβ-induced RS production, elevated NADPH oxidase activity, interaction with mitochondria-associated Aβ alcohol dehydrogenase, inhibition of cytochrome oxidase (respiratory complex IV), and by causing leakage of electrons from the mitochondrial electron transport chain (Hensley et al., 1994; Canevari et al., 1999; L”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Canevari et al., 1999
A similar amyloid fragment has been reported to impair mitochondrial function in isolated brain mitochondria.
“A similar amyloid fragment has been reported to impair mitochondrial function in isolated brain mitochondria (Canevari et al., 1999).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Canevari et al., 1999
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- Authors
- Canevari, L., Clark, J. B., & Bates, T. E.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Corresponding author
- Canevari, Laura
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1999-08-20
- Volume
- 457
- Issue
- 1
- Pages
- 131-134
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2067656585
- Cited by
- 196
- References
- 2
- Citations by year
- 2026: 12 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 4 · 2013: 6 · 2012: 12
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- cytochrome c oxidase, mitochondrial respiratory chain, Alzheimer's disease, amyloid precursor protein, mitochondrial oxidative metabolism, brain mitochondria, citrate synthase
- MeSH terms
- Animals, Brain, Citrate (si)-Synthase, Electron Transport Complex IV, Electron Transport, Kinetics, Male, Mitochondria, Time Factors, Amyloid beta-Peptides, Rats, Wistar, Neurodegenerative Diseases, Rats
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