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Cited by 469Alzheimer's disease research and treatmentsMitochondrial Function and PathologyNeurological Disorders and Treatments

Mitochondria-targeted antioxidants protect against amyloid-β toxicity in Alzheimer's disease neurons

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Manczak, Maria, Mao, Peizhong, Calkins, Markus J., Cornea, Anda, Reddy, Arubala P., Murphy, Michael P., Szeto, Hazel H., Park, Byung +1 more·2010·Journal of Alzheimer's Disease
DOI 10.3233/jad-2010-100564PMC PMC3072711
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Abstract

The purpose of our study was to investigate the effects of the mitochondria-targeted antioxidants, MitoQ and SS31, and the anti-aging agent resveratrol on neurons from a mouse model (Tg2576 line) of Alzheimer's disease (AD) and on mouse neuroblastoma (N2a) cells incubated with the amyloid-beta (Abeta) peptide. Using electron and confocal microscopy, gene expression analysis, and biochemical methods, we studied mitochondrial structure and function and neurite outgrowth in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Abeta. In N2a cells only incubated with the Abeta, we found increased expressions of mitochondrial fission genes and decreased expression of fusion genes and also decreased expression of peroxiredoxins. Electron microscopy of the N2a cells incubated with Abeta revealed a significantly increased number of mitochondria, indicating that Abeta fragments mitochondria. Biochemical analysis revealed that function is defective in mitochondria. Neurite outgrowth was significantly decreased in Abeta-incubated N2a cells, indicating that Abeta affects neurite outgrowth. However, in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Abeta, abnormal expression of peroxiredoxins and mitochondrial structural genes were prevented and mitochondrial function was normal; intact mitochondria were present and neurite outgrowth was significantly increased. In primary neurons from amyloid-beta precursor protein transgenic mice that were treated with MitoQ and SS31, neurite outgrowth was significantly increased and cyclophilin D expression was significantly decreased. These findings suggest that MitoQ and SS31 prevent Abeta toxicity, which would warrant the study of MitoQ and SS31 as potential drugs to treat patients with AD.

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Authors
Manczak, M., Mao, P., Calkins, M. J., Cornea, A., Reddy, A. P., Murphy, M. P., Szeto, H. H., Park, B., & Reddy, P. H.
Affiliations
  • Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA
  • Oregon National Primate Research Center (US)
  • MRC Mitochondrial Biology Unit (GB)
  • Cornell University (US)
  • Oregon Health & Science University (US)
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2010-06-03
Volume
20
Issue
s2
Pages
S609-S631
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-2010-100564
PMC
PMC3072711
OpenAlex
W2000742321
Cited by
469
References
10
Citations by year
2026: 17 · 2025: 18 · 2024: 29 · 2023: 28 · 2022: 26 · 2021: 39 · 2020: 25 · 2019: 26 · 2018: 34 · 2017: 36 · 2016: 35 · 2015: 21 · 2014: 33 · 2013: 26 · 2012: 40
FWCI
20.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Oregon Health and Science University
  • University of Minnesota
  • National Institutes of Health (RR 00163)
  • National Institute on Aging (AG026051, R03AG026051, R01AG028072, AG028072)
  • National Center for Research Resources (P51RR000163, K01RR000163, RR-00163.)
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 › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
Alzheimer's disease, amyloid-beta toxicity
MeSH terms
Adenosine Triphosphate, Alzheimer Disease, Analysis of Variance, Animals, Antioxidants, Cell Line, Transformed, Cell Survival, Electron Transport Complex IV, Disease Models, Animal, Drug Interactions, Gene Expression Regulation, Humans, Hydrogen Peroxide, Mice, Transgenic, Mitochondria, Neurons, Peptide Fragments, RNA, Messenger, Lipid Peroxidation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mitochondrial Proteins, Microscopy, Electron, Transmission, Mice, Membrane Potential, Mitochondrial, Peroxiredoxins

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