The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice

Young, Melissa L.; Franklin, James L.

doi:10.1016/j.mcn.2019.103409

Cited by 120Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice

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Young, Melissa L., Franklin, James L.·2019·Molecular and Cellular Neuroscience

DOI 10.1016/j.mcn.2019.103409PMC PMC7359863

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Abstract

Oxidative stress, likely stemming from dysfunctional mitochondria, occurs before major cognitive deficits and neuropathologies become apparent in Alzheimer's disease (AD) patients and in mouse models of the disease. We previously reported that treating 2- to 7-month-old 3xTg-AD mice with the mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-Dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl](triphenyl)phosphonium methanesulfonate), a period when AD-like pathologies first manifest in them, prevents AD-like symptoms from developing. To elucidate further a role for mitochondria-derived oxidative stress in AD progression, we examined the ability of MitoQ to inhibit AD-like pathologies in these mice at an age in which cognitive and neuropathological symptoms have fully developed. 3xTg-AD female mice received MitoQ in their drinking water for five months beginning at twelve months after birth. Untreated 18-month-old 3xTg-AD mice exhibited significant learning deficits and extensive AD-like neuropathologies. MitoQ-treated mice showed improved memory retention compared to untreated 3xTg-AD mice as well as reduced brain oxidative stress, synapse loss, astrogliosis, microglial cell proliferation, Aβ accumulation, caspase activation, and tau hyperphosphorylation. Additionally, MitoQ treatment significantly increased the abbreviated lifespan of the 3xTg-AD mice. These findings support a role for the involvement of mitochondria-derived oxidative stress in the etiology of AD and suggest that mitochondria-targeted antioxidants may lessen symptoms in AD patients.

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These findings support the idea that targeting mitochondria to relieve symptoms in patients with Alzheimer disease is worthwhile.
“These findings support the idea that targeting mitochondria to relieve symptomology in patients with Alzheimer disease is worthwhile.”
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Self-citation
The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease
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Authors: Young, M. L., & Franklin, J. L.
Affiliations: University of Georgia (US)
Corresponding author: Franklin, James L.
ORCID: Franklin, James L.
Venue: Molecular and Cellular Neuroscience
Publisher: Elsevier BV
Published: 2019-12
Volume: 101
Pages: 103409
ISSN: 1044-7431 (ISSN-L)
DOI: 10.1016/j.mcn.2019.103409
PMC: PMC7359863
OpenAlex: W2972942048
Cited by: 120
References: 97
Citations by year: 2026: 15 · 2025: 24 · 2024: 20 · 2023: 16 · 2022: 19 · 2021: 11 · 2020: 11 · 2019: 4
FWCI: 7.72
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Molecular and Cellular Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
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 › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: MitoQ, mitochondria-targeted antioxidants, Alzheimer's disease, 3xTg-AD mice, oxidative stress, mitochondrial dysfunction, memory loss, lifespan extension, amyloid-beta deposition, tau hyperphosphorylation, synaptic loss, astrocyte activation, microglial proliferation, caspase activation, aging
MeSH terms: Alzheimer Disease, Animals, Antioxidants, Brain, Female, Gliosis, Longevity, Male, Memory, Mice, Inbred C57BL, Mitochondria, Organophosphorus Compounds, Ubiquinone, Apoptosis, Oxidative Stress, Mice

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The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice

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