Oxidative stress, redox signalling and endothelial dysfunction in ageing‐related neurodegenerative diseases: a role of <scp>NADPH</scp> oxidase 2

Cahill-Smith, Sarah; Li, Jian-Mei

doi:10.1111/bcp.12357

Cited by 95 publications

(73 citation statements)

References 161 publications

(170 reference statements)

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“…Alzheimer’s disease (AD) is characterized by progressive memory loss, cognitive and executive impairment, with varying degrees of aphasia, apraxia, and agnosia [98, 192]. Early in AD progression, cognitive symptoms are caused by damage to the hippocampus [193, 194].…”

Section: Introductionmentioning

confidence: 99%

NADPH oxidase in brain injury and neurodegenerative disorders

Merry

Wang

Zhang

et al. 2017

Mol Neurodegeneration

329

309

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Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology. NADPH oxidase has the primary function to generate free radicals. In particular, there is growing evidence that the isoforms NOX1, NOX2, and NOX4 can be upregulated by a variety of neurodegenerative factors. The majority of recent studies have shown that genetic and pharmacological inhibition of NADPH oxidase enzymes are neuroprotective and able to reduce detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. This review aims to summarize evidence supporting the role of NADPH oxidase in the pathology of these neurological disorders, explores pharmacological strategies of targeting this major oxidative stress pathway, and outlines obstacles that need to be overcome for successful translation of these therapies to the clinic.

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Section: Introductionmentioning

confidence: 99%

NADPH oxidase in brain injury and neurodegenerative disorders

Merry

Wang

Zhang

et al. 2017

Mol Neurodegeneration

329

309

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“…[1][2][3][4][5] ROS can be divided into radical species (eg, ÁOH) and nonradical species (eg, H 2 O 2 ). They are mainly produced by several different enzyme systems (eg, cytosolic enzyme) and by the mitochondrial complex I and III.…”

mentioning

confidence: 99%

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

Tain

Scotti

et al. 2017

Magnetic Resonance Imaging

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Purpose: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). Materials and Methods: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T 1 and T 2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H 2 O 2 ) were used to evaluate the effect of produced ROS in T 1 and T 2 for up to 4 hours. pH and temperature changes due to H 2 O 2 treatment in egg white were also monitored. The influences from H 2 O 2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T 1 in H 2 O 2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T 1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n 5 6). Results: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <18C, respectively). T 1 relaxation time in the H 2 O 2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T 2 (<10%). In the H 2 O 2 -treated BSA solution that produce no ROS, there was a small change in T 1 due to H 2 O 2 itself (61%), although a significant T 2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T 1 (13 6 1%) and T 2 (1 6 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T 1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 3 10 7 vs. 0.9 s 21 ÁmM 21 ). Finally, significantly reduced T 1 was observed in rotenone-treated mouse brain (5.1 6 2.5%, P < 0.05). Conclusion: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. Level of Evidence: 2 Technical Efficacy Stage: 2 J. MAGN. RESON. IMAGING 2018;47:222-229. R eactive oxygen species (ROS), including singlet oxygen, and hydroxyl radical (ÁOH), have long been subjects of study due to their central role in cell signaling, the aging process, and in the pathogenesis of a variety of diseases such as cardiovascular diseases, diabetes, cancer, Alzheimer's, and Parkinson's diseases. 1-5 ROS can be divided into radical species (eg, ÁOH) and nonradical species (eg, H 2 O 2 ). They are mainly produced by several different enzyme systems (eg, cytosolic enzyme) and by the mitochondrial complex I and III. 6 They can react readily with any surrounding tissue component (eg, lipids, proteins, and DNA) 2 and can initiate complicated chain processes with high biological impact (eg, Haber-Weiss or Fenton reactions). 7 The high reactivity and short lifetime of radical ROS make them very challenging to detect. For example, the lifetime...

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“…Microglia and astrocytes release inflammatory mediators in response to oxidative stress (Cahill-Smith and Li, 2014;Chiurchiu and Maccarrone, 2011;Fuller et al, 2010). Reactive oxygen species (ROS) can activate inflammatory responses in the CNS by stimulating redox-sensitive transcription factors, including the nuclear factor κB and activator protein-1 (AP-1) (Chiurchiu and Maccarrone, 2011).…”

Section: Pathologies and Neuroinflammationmentioning

confidence: 99%

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

Rodríguez‐Ramírez¹,

Adalid‐Peralta²,

Fragoso³

et al. 2015

JCI

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A complex, highly specialized immunomodulatory microenvironment exists in the central nervous system, as a number of protective mechanisms against insults of different kinds have evolved over time to help in maintaining homoeostasis in this compartment.Inflammation in the central nervous system (neuroinflammation) is an elaborate process, triggered in response to challenges of diverse nature. Characterized by increased glial activation (phagocytic phenotype) and the production of pro-inflammatory cytokines, it often leads to blood-brain barrier disruption and leukocyte invasion. While the initial response to an injury involving oxidative and nitrosative stress usually causes acute neuroinflammation, it seldom affects long-term neuronal survival. Chronic neuroinflammation, on the other side, may affect cell survival and brain functions, as observed in several neurodegenerative disorders. Various peripheral and central injuries can alter the homeostasis in the central nervous system, triggering a persistent adaptive inflammatory response that could lead to a vicious circle of neuronal damage.The purpose of this review is to describe the most relevant players in this phenomenon, and to highlight their detrimental role in different neurologic diseases.

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Oxidative stress, redox signalling and endothelial dysfunction in ageing‐related neurodegenerative diseases: a role of NADPH oxidase 2

Cited by 95 publications

References 161 publications

NADPH oxidase in brain injury and neurodegenerative disorders

NADPH oxidase in brain injury and neurodegenerative disorders

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

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