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

08:00 EDT 12th September 2019 | BioPortfolio

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

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.


Journal Details

This article was published in the following journal.

Name: Molecular and cellular neurosciences
ISSN: 1095-9327
Pages: 103409


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Medical and Biotech [MESH] Definitions

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A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.

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