Coenzyme Q10 Attenuates β-Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation

Yang, Xifei; Yang, Ying; Li, Geng; Wang, Jian‐Zhi; Yang, E.S.

doi:10.1007/s12031-007-9033-7

Cited by 100 publications

(64 citation statements)

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“…The antioxidants are potential therapeutics by eliminating ROS and exerting neuroprotective effects on neurons in AD properties both in vitro and in vivo [113] ; its administration to transgenic AD mice also dramatically reduces the amyloid plaque burden [114,115] . Although CoQ10 has not been tested in clinic trials, its analog, idebenone, has been assessed in AD patients, and has beneficial effects on memory and attention [116,117] .…”

Section: Antioxidants As a Treatment For Alzheimer's Diseasementioning

confidence: 99%

Oxidative stress in Alzheimer’s disease

2014

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Oxidative stress plays a significant role in the pathogenesis of Alzheimer's disease (AD), a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons (lipids, proteins, and nucleic acids) can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, infl ammation, and β-amyloid (Aβ) peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.Keywords: Alzheimer's disease; oxidative stress; β-amyloid; tau; metals; antioxidants ·Review· IntroductionThe human brain, although it constitutes only 2% of the body weight, consumes ~20% of the oxygen supplied by the respiratory system [1] . The high energy-consumption of the brain means that it is more susceptible to oxidative stress than any other organ. As the basic functional unit of the brain, the neuron is particularly vulnerable to oxidative damage because it has a higher metabolic rate than other cells [2] . The oxidation of lipids, proteins, and nucleic acids in neurons is a common pathological feature of Alzheimer's disease (AD) [3] . Neurons contain a large amount of polyunsaturated fatty acids (PUFAs) that can interact with reactive oxygen species (ROS), leading to a selfpropagating cascade of lipid peroxidation and molecular destruction [4] . Furthermore, neurons contain low levels of glutathione, an essential antioxidant for eliminating free radicals [5] . Therefore, neurons are highly susceptible to oxidative stress.An increased oxidative burden has been reported in the brains of non-demented elderly and/or sporadic AD patients [6,7] . Increased levels of oxidative stress biomarkers in the blood reflect such stress in the brain [8,9] . Currently, many blood markers of oxidative stress have been identified in AD patients or related animal models, including protein carbonyls and 3-nitrotyrosine [10,11] , , malondialdehyde (MDA) [12] , 4-hydroxynonenal (4-HNE), and F2-isoprostanes (F2-IsoPs) [13][14][15][16] . Apart from the intracellular accumulation of free radicals, changes in the activities or expressions of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, have also been described in both the central nervous system and peripheral tissues of AD patients [14,17] . Thus, oxidative stress is an important pathological feature in AD.However, how and where the oxidative stress originates in AD are open questions. Research has suggested that mitochondrial dysfunction [12,18,19] , metal accumulation [12,20,21] , hyperphosphorylated tau [22,23] , inflammation [24,25] , and β-amyloid (Aβ) accumulation [12,19] are the basic mechanisms underlying the induction of oxidative stress. Deficiency or destruction of components of the antioxidant system such as SOD in the mi...

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Section: Antioxidants As a Treatment For Alzheimer's Diseasementioning

confidence: 99%

Oxidative stress in Alzheimer’s disease

2014

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“…1 CoQ 10 supplementation also decreased the MDA level and attenuated beta-amyloid pathology in an Alzheimer disease model. 25 In addition, previous studies using a cerebral ischemia model indicate that CoQ 10 exerts a neuroprotective effect by attenuating the severity of oxidative stress. 16,17 In a rat model of cerebral ischemia induced by endothelins, CoQ 10 effectively diminished neuronal injury by decreasing free radical concentration.…”

Section: Discussionmentioning

confidence: 99%

“…CoQ 10 has been widely postulated to have neuroprotective properties, and administration of exogenous CoQ 10 has been shown to exert neuroprotective effects in various models of CNS disorders, including neurodegenerative disease, 13,25 epilepsy, 1 and ischemic injury. 17,18,26 In a preliminary clinical trial, CoQ 10 treatment after cardiac arrest improved survival rate and neurological outcomes in survivors when combined with mild hypothermia.…”

Section: Discussionmentioning

confidence: 99%

“…6,23 Our findings, which demonstrated the decreased oxidative stress following CoQ 10 administration, agree with previous studies that used various cerebral injury models. 1,10,25 In an experimental traumatic brain injury model, the group treated with CoQ 10 after head trauma showed significantly lower MDA levels and attenuated neuronal damage compared with the control group. 10 In an animal model of temporal lobe epilepsy, CoQ 10 pretreatment effectively reduced the increase of kainate-induced intrahippocampal MDA level and attenuated hippocampal neuronal loss.…”

Section: Discussionmentioning

confidence: 99%

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Effect of coenzyme Q10 on spinal cord ischemia-reperfusion injury

Hwang

Min

Jeon

et al. 2015

SPI

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OBJECT Spinal cord ischemia remains a serious complication of thoracoabdominal aortic aneurysm surgery. Coenzyme Q10, a potent antioxidant, has been reported to exert a neuroprotective effect. In the present study, we evaluated the effect of coenzyme Q10 pretreatment on spinal cord ischemia-reperfusion injury. METHODS Male Sprague-Dawley rats were treated with either 300 mg/kg coenzyme Q10 (CoQ10 group, n = 12) or saline (control and sham groups, n = 12 for each group) for 5 days before ischemia. Spinal cord ischemia was induced in the control and CoQ10 groups. Neurological function was assessed using the Basso-Beattie-Bresnahan (BBB) motor rating scale until 7 days after reperfusion, and then the spinal cord was harvested for histopathological examinations and an evaluation of malondialdehyde level. RESULTS On post-reperfusion Day 1, the CoQ10 group showed higher BBB scores compared with those in the control group, although the difference was not significant. However, on Day 2, the CoQ10 group showed a significantly higher BBB score than the control group (14.0 [10.3–15.0] vs 8.0 [5.0–9.8], median [IQR], respectively; p = 0.021), and this trend was maintained until Day 7 (17.5 [16.0–18.0] vs 9.0 [6.5–12.8], respectively; p < 0.001). Compared with the control group, the CoQ10 group had more normal motor neurons (p = 0.003), fewer apoptotic changes (p = 0.003) and a lower level of tissue malondialdehyde (p = 0.024). CONCLUSIONS Pretreatment with 300 mg/kg coenzyme Q10 resulted in significantly improved neurological function and preservation of more normal motor neurons.

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“…In addition, increased levels of malondialdehyde and downregulation of SOD, both markers of oxidative stress seen in the transgenic mice, were ameliorated by CoQ10 treatment. 73 Supplemental CoQ10 was also found to attenuate brain atrophy at 60 days, as assessed by MRI in vivo, in aged transgenic mice with amyloid precursor protein (APP) mutations. Single transgenic APP and presenilin 1 (PS1) mice as well as double transgenic APP/PS1 mice were treated with 2,400 mg/kg/day or placebo.…”

Section: Coq10 Effects In Healthy Animals and Animal Models Of Neurodmentioning

confidence: 99%