Ceruloplasmin, a Potential Therapeutic Agent for Alzheimer's Disease

Zhao, Yihong; Zhang, Li Hong; Gou, Yu Jing; Zhao, Jing; You, Lin; Wang, Zhan You; Zheng, Xin; Yan, Liang; Yu, Peng; Chang, Yan

doi:10.1089/ars.2016.6883

Cited by 29 publications

(30 citation statements)

References 42 publications

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“…We investigated whether H 2 -O 2 mixture enhanced the antioxidant capacity to protect against CIH-induced oxidative stress injury. SOD and GSH are essentially endogenous antioxidants that scavenge superoxide anion radicals and hydrogen peroxide [30]. T-SOD and GSH activities were substantially elevated in the CIH+H 2 group compared to the CIH group (Figures 5(a) and 5(b)).…”

Section: Resultsmentioning

confidence: 99%

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Zhao

Yang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O2 (FiO2) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H2-O2 mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H2-O2 mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H2-O2 mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H2-O2 mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H2-O2 mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H2-O2 mixture significantly reduced ER stress and apoptosis and that H2 might be an efficient antioxidant against the oxidative stress injury induced by CIH.

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Section: Resultsmentioning

confidence: 99%

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Zhao

Yang

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…We then evaluated whether Ndfip1 played a role in protecting against iron-induced cell injury, and the results revealed that excessive iron aggravated neuronal injury, whereas Ndfip1 overexpression reversed iron-induced cell damage. Several studies have demonstrated that reduction of brain iron accumulation is a potential strategy for AD prevention (Zheng et al, 2009 ; Guo et al, 2013a , b ; Zhang et al, 2018 ; Zhao et al, 2018 ). However, further studies are needed to evaluate whether regulation of brain iron homeostasis through enhancing Ndfip1 protein level is benefit for blocking the neuropathological process of AD.…”

Section: Discussionmentioning

confidence: 99%

Lower Expression of Ndfip1 Is Associated With Alzheimer Disease Pathogenesis Through Decreasing DMT1 Degradation and Increasing Iron Influx

Tian

Zheng

et al. 2018

Front. Aging Neurosci.

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We have previously reported that high expression of divalent metal transporter 1 (DMT1) plays a crucial role in iron dyshomeostasis and β-amyloid (Aβ) peptide generation in the brain of Alzheimer’s disease (AD). Recent studies have shown that Nedd4 family interacting protein 1 (Ndfip1) can degrade DMT1 through ubiquitination pathway and reduce the accumulation of intracellular iron. The present study aims to evaluate whether Ndfip1 is involved in AD pathogenesis through mediating DMT1 degradation and iron metabolism. β-amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mouse and Ndfip1 transfected SH-SY5Y cells were used in this study. Immunohistochemistry and Western blot were performed to examine the distribution and expression levels of Ndfip1 and DMT1. In addition, ELISA and calcein fluorescence were carried out for analyzing the levels of Aβ peptide and iron influx, respectively. The results showed that Ndfip1 immunoreactivity was decreased in the cortex and hippocampus of APP/PS1 mice, compared with wild type (WT) controls. Colocalization of Ndfip1 and Aβ within senile plaques could be observed. Immunoblot analyses showed that low expression of Ndfip1 and high expression of DMT1 proteins were detected in APP/PS1 mouse brain, compared with age-matched WT animals. Overexpression of Ndfip1 down-regulated DMT1 expression, and reduced iron influx and Aβ secretion in SH-SY5Y cells. Further, overexpressed Ndfip1 significantly attenuated iron-induced cell damage in Ndfip1 transfected cells. The present study suggests that lower expression of Ndfip1 might be associated with the pathogenesis of AD, through decreasing DMT1 degradation and increasing iron accumulation in the brain.

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“…Animal usage was approved by California Medical Innovations Institute (CalMI2) Institutional Animal Care and Use Committee (IACUC). The genotyping was conducted in CalMI2 animal facilities at the age of 21 days by tail DNA extraction according to our previous protocol and the online information supplied by the vendor. Eleven mice per strain (3xTg‐AD, B6129SF2/J) at the ages of 6, 9 and 12 mo were used in this study.…”

Section: Methodsmentioning

confidence: 99%

Cerebrovascular miRNAs correlate with the clearance of Aβ through perivascular route in younger 3xTg‐AD mice

Jiang

Weng

et al. 2019

Brain Pathology

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The “two‐hit vascular hypothesis for Alzheimer's disease (AD)” and amyloid‐β (Aβ) oligomer hypothesis suggest that impaired soluble Aβ oligomers clearance through the cerebral vasculature may be an initial step of the AD process. Soluble Aβ oligomers are driven into perivascular spaces from the brain parenchyma and toward peripheral blood flow. The underlying vascular‐based mechanism, however, has not been defined. Given that microRNAs (miRNAs), emerging as novel modulators, are involved in numerous physiological and pathological processes, we hypothesized that cerebrovascular miRNAs may regulate the activities of brain blood vessels, which further affects the concentration of Aβ in the AD brain. In this study, perivascular Aβ deposits, higher vascular activation, increased pericyte coverage and up‐regulated capillaries miRNAs at 6 months old (6 mo) were found to correlate with the lower Aβ levels of middle AD stage (9 mo) in 3xTg‐AD (3xTg) mice. It is implicated that at the early stage of AD when intracellular Aβ appeared, higher expression of vessel‐specific miRNAs, elevated pericyte coverage, and activated endothelium facilitate Aβ oligomer clearance through the perivascular route, resulting in a transient reduction of Aβ oligomers at 9 mo. Additionally, ghrelin‐induced upregulation of capillary miRNAs and increased pericyte coverage attenuated Aβ burden at 9 mo, in further support of the relationship between vascular miRNAs and Aβ clearance. This work suggests a cerebral microvessel miRNA may boost endothelial highly activated phenotypes to promote elimination of Aβ oligomers through the perivascular drainage pathway and contribute to AD progression. The targeting of brain vessel‐specific miRNAs may provide a new rationale for the development of innovative therapeutic strategies for AD treatment.

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Ceruloplasmin, a Potential Therapeutic Agent for Alzheimer's Disease

Abstract: Our results show a protective role of CP in AD and suggest that regulating CP expression in the hippocampus may provide a new neuroprotective strategy for AD. Antioxid. Redox Signal. 28, 1323-1337.

Cited by 29 publications

References 42 publications

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Lower Expression of Ndfip1 Is Associated With Alzheimer Disease Pathogenesis Through Decreasing DMT1 Degradation and Increasing Iron Influx

Cerebrovascular miRNAs correlate with the clearance of Aβ through perivascular route in younger 3xTg‐AD mice

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