Amyloid ?? peptide induces cytochrome c release from isolated mitochondria
Abstract
Amyloid beta peptide (Abeta) is a neurotoxic metabolic product of the amyloid precursor protein (APP). Abeta is strongly implicated in the pathology of Alzheimer's disease (AD) and can be formed intracellularly. In this study, we show that the addition of Abeta to isolated mouse brain mitochondria can directly induce cytochrome c (Cyt c) release and mitochondrial swelling, which were partially inhibited by cyclosporin A (CsA). These results suggest that the Abetaaccumulated intracellularly by APP processing might exert neurotoxicity by interacting with mitochondria and inducing mitochondrial swelling and release of Cyt c, which activates caspase-3 and finally can lead to apoptosis in neuronal cells and to neurodegeneration in AD.
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Aβ and its precursor APP localize, in part, to mitochondria in which they can cause mitochondrial dysfunction as evidenced by increased production of RS, enzyme inhibition, loss of cytochrome c, and depolarization of Δψm.
“Aβ, and its precursor APP, localize, in part, to mitochondria in which they can cause mitochondrial dysfunction as evidenced by increased production of RS, enzyme inhibition, loss of cytochrome c, and depolarization of Δψm (Casley et al., 2002a; Kim et al., 2002; Anandatheerthavarada et al., 2003; Jang and Surh, 2003; Lustbader et al., 2004; Liang et al., 2009; Takuma et al., 2009).”
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 Kim et al., 2002
Cites
Intraneuronal Aβ42 Accumulation in Human Brain
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Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease
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“Interestingly, Aβ42 has been shown to cause cytochrome c release from mitochondria [45], which activates Caspase-3 and induces apoptosis, thus providing a potential mechanism for intraneuronal Aβ42-mediated neuron loss in 5XFAD mice.”
BackgroundThe role of mitochondrial dysfunction in age-related diseases
Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205 · see citing works
Can a Bacterial Endotoxin be a Key Factor in the Kinetics of Amyloid Fibril Formation?
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MicroRNA-338-5p alleviates neuronal apoptosis via directly targeting BCL2L11 in APP/PS1 mice.
Li, J., Li, D., Zhou, H., Wu, G., He, Z., Liao, W., Li, Y., & Zhi, Y. (2020) · Aging · doi:10.18632/aging.104005 · Cited by 35 · see citing works
“Intriguingly, cytochrome c released from mitochondria was caused by Aβ42 [47], which activated Caspase-3 activity and induced apoptosis, thus providing a potential mechanism for intraneuronal neuron loss induced by Aβ42.”
BackgroundInfluential
- Authors
- Kim, H.-S., Lee, J.-H., Lee, J.-P., Kim, E.-M., Chang, K.-A., Park, C. H., Jeong, S.-J., Wittendorp, M. C., Seo, J.-H., Choi, S.-H., & Suh, Y.-H.
- Affiliations
- Seoul National University (KR)
- Harvard University (US)
- Corresponding author
- Kim, Hye-Sun
- Lee, Jun-Ho
- Lee, Jean-Pyo
- ORCID
- Venue
- NeuroReport
- Published
- 2002-10
- Volume
- 13
- Issue
- 15
- Pages
- 1989-1993
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W1981487415
- Cited by
- 124
- References
- 2
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › 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 › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- amyloid-beta, cytochrome c release, mitochondrial swelling, cyclosporine, caspase-3 activation, apoptosis, neurotoxicity, Alzheimer's disease, amyloid precursor protein, brain mitochondria, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Membrane Permeability, Cells, Cultured, Cytochrome c Group, Enzyme Inhibitors, Humans, Mitochondria, Neurons, Peptide Fragments, Amyloid beta-Peptides, Cyclosporine, Apoptosis, Calcium Signaling, Caspases, Mice, Caspase 3
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