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 81 publications

(31 citation statements)

References 83 publications

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“…Synaptic dysfunction, including LTP deficits, occurs prior to plaques and tangles. Furthermore, cognitive deficits are evident at four months of age [27], while oxidative stress precedes these impairments, comprising some of the earliest pathological signs noted in this animal model of AD [28,29].…”

Section: Introductionmentioning

confidence: 83%

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Beggiato

Tomasini

Cassano

et al. 2020

JCM

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N-palmitoylethanolamide (PEA) is a lipid mediator belonging to the class of the N-acylethanolamine. Products containing PEA, also in ultramicronized formulation (um-PEA), are already licensed for use in humans for its analgesic and anti-inflammatory properties, and demonstrated high safety and tolerability. Preclinical studies indicate that PEA, especially in the ultramicronized form, could be a potential therapeutic agent for Alzheimer’s disease (AD). In this study, we evaluated the neuroprotective and antioxidant effects of chronic (three months) um-PEA administration in an animal model of AD (3×Tg-AD mice). For translation purposes, the compound has been orally administered. Cognitive performance as well as biochemical markers [(interleukin-16 (IL-16) and tumor necrosis factor-α (TNF-α)] levels, reactive oxygen species (ROS) production, synaptophysin and glutamate levels) have been evaluated at the end of um-PEA treatment. The results indicate that orally administered um-PEA was adsorbed and distributed in the mice brain. The chronic treatment with um-PEA (100 mg/kg/day for three months) rescued cognitive deficit, restrained neuroinflammation and oxidative stress, and reduced the increase in hippocampal glutamate levels observed in 3×Tg-AD mice. Overall, these data reinforce the concept that um-PEA exerts beneficial effects in 3×Tg-AD mice. The fact that PEA is already licensed for the use in humans strongly supports its rapid translation in clinical practice.

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Section: Introductionmentioning

confidence: 83%

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Beggiato

Tomasini

Cassano

et al. 2020

JCM

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“…NO. : HY-100116A) 47 , ML385 (Nrf2 inhibitor, catalogue number: HY-100523) and bardoxolone (Nrf2 activator, catalogue number: HY-14909) were obtained from MCE China (Shanghai, China). High fat high sucrose diet (HFS):nutrient components: 18% fat, 20% sucrose, 2% cholesterol, 0.2% cholate, 59.8% normal diet; calorie percentage:44.5% fat,16.5% sucrose,8% protein,30.9% carbohydrate (Tengxin Biotechnology Inc., Chongqing, China).…”

Section: Methods Chemicals and Reagents Cvb-d (Purity >98%mentioning

confidence: 99%

Cyclovirobuxine D protects against diabetic cardiomyopathy by activating Nrf2-mediated antioxidant responses

Jiang

et al. 2020

Sci Rep

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Diabetic cardiomyopathy (DCM) is the principal cause of death in people with diabetes. However, there is currently no effective strategy to prevent the development of DCM. Although cyclovirobuxine D (CVB-D) has been widely used to treat multiple cardiovascular diseases, the possible beneficial effects of CVB-D on DCM remained unknown. The present aim was to explore the potential effects and underlying mechanisms of CVB-D on DCM. We explored the effects of CVB-D in DCM by using high fat high sucrose diet and streptozotocin-induced rat DCM model. Cardiac function and survival in rats with DCM were improved via the amelioration of oxidative damage after CVB-D treatment. Our data also demonstrated that pre-treatment with CVB-D exerted a remarkable cytoprotective effect against high glucose-or H 2 o 2-induced neonatal rat cardiomyocyte damage via the suppression of reactive oxygen species accumulation and restoration of mitochondrial membrane potential; this effect was associated with promotion of Nrf2 nuclear translocation and its downstream antioxidative stress signals (NQO-1, Prdx1). Overall, the present data has provided the first evidence that CVB-D has potential therapeutic in DCM, mainly by activation of the Nrf2 signalling pathway to suppress oxidative stress. Our findings also have positive implications on the novel promising clinical applications of CVB-D. Diabetic cardiomyopathy (DCM) is usually characterised by cardiac structure and functional disorders in individuals with diabetes independent of hypertension or ischemic coronary artery disease 1-3. Although it is the principal cause of death in patients with diabetes, no effective strategies currently exist to prevent the progression of DCM 4. The pathogenesis of DCM involves in many factors such as oxidative stress, chronic low-grade inflammation 5 , autophagy 6 , and pyroptosis 7 , etc. The accumulated evidences confirm that cardiomyocyte injuries induced by oxidative stress are the predominant contributors to the pathophysiological process of DCM 8. Reactive oxygen species (ROS) overproduction induced by hyperglycaemia, free fatty acids, and glycosylation end products results in myocardial structural damage and functional or metabolic disorders, which are considered to be the key pathological signal of DCM 9. Therefore, amelioration of oxidative stress may be a therapeutic strategy to prevent the progression of DCM. Nuclear factor (carotenoid-derived 2)-like 2 (Nrf2) is the major transcription factor in the cellular antioxidant response 10. The expression and activity of Nrf2 are regulated by cullin 3-based ubiquitin E3 ligases, such as Kelch-like ECH-related protein 1 (Keap1). Upon exposure to various stress conditions, Nrf2 is uncoupled from

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“…In an Alzheimer’s disease (AD) mouse model, MitoQ treatment significantly improved spatial memory retention and reduced brain oxidative stress, astrogliosis, microglia cell proliferation, tau hyper-phosphorylation, and amyloid plaque formation [ 90 ]. MitoQ treatment also extended the lifespan of 3xTg-AD mice, thus emphasizing its role in dampening the neuropathology responsible for the accelerated death rate of these mice.…”

Section: Therapeutic Options Targeting Oxidative Stress In Tbimentioning

confidence: 99%

Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

et al. 2020

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Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

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

Cited by 81 publications

References 83 publications

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Cyclovirobuxine D protects against diabetic cardiomyopathy by activating Nrf2-mediated antioxidant responses

Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

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