Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis

Liu, Rugao; Althaus, John S.; Ellerbrock, Brenda R.; Becker, Dávid; Gurney, Mark E.

doi:10.1002/ana.410440510

Cited by 152 publications

(106 citation statements)

References 31 publications

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“…Both sALS and fALS are clinically indistinguishable and show similar features. The molecular mechanisms responsible for disease pathogenesis and progression are still unknown; however, studies have shown that patients with fALS have mutations in copper/zinc (Cu/Zn) superoxide dismutase (SOD1), a relevant component of the antioxidant defense system (254). More than 100 SOD1 mutations have been identified in fALS patients (13), most of which result from substitution of one single amino acid, such as SOD1 G85R , SOD1 G37R , and SOD1…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

157

142

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

157

142

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“…Oxidative stress is described as one of the possible major causes of motoneuronal death in ALS (Liu et al, 1998). To test whether HDACi treatment could be used as a therapeutic approach to prevent MN death in ALS mice, we first used a simplified cellular model, the NSC34 cell line, a hybridoma of spinal cord motoneurons and neuroblastoma (Cashman et al, 1992), in which cell death can be induced by oxidative stress (Cookson et al, 1998).…”

Section: Hdaci Protects From Oxidative Stress-induced Mn Deathmentioning

confidence: 99%

Sodium Valproate Exerts Neuroprotective EffectsIn Vivothrough CREB-Binding Protein-Dependent Mechanisms But Does Not Improve Survival in an Amyotrophic Lateral Sclerosis Mouse Model

Rouaux

Panteleeva²,

Frydman³

et al. 2007

J. Neurosci.

200

137

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Amyotrophic lateral sclerosis (ALS) is characterized by motoneuron (MN) degeneration, generalized weakness, and muscle atrophy. The premature death of MNs is thought to be a determinant in the onset of this disease. In a transgenic mouse model of ALS expressing the G86R mutant superoxide dismutase 1 (mSOD1), we demonstrated previously that CREB (cAMP response element-binding protein)-binding protein (CBP) and histone acetylation levels were specifically decreased in nuclei of degenerating MNs. We show here that oxidative stress and mSOD1 overexpression can both impinge on CBP levels by transcriptional repression, in an MN-derived cell line. Histone deacetylase inhibitor (HDACi) treatment was able to reset proper acetylation levels and displayed an efficient neuroprotective capacity against oxidative stress in vitro. Interestingly, HDACi also upregulated CBP transcriptional expression in MNs. Moreover, when injected to G86R mice in vivo, the HDACi sodium valproate (VPA) maintained normal acetylation levels in the spinal cord, efficiently restored CBP levels in MNs, and significantly prevented MN death in these animals. However, despite neuroprotection, mean survival of treated animals was not significantly improved (Ͻ5%), and they died presenting the classical ALS symptoms. VPA was not able to prevent disruption of neuromuscular junctions, although it slightly delayed the onset of motor decline and retarded muscular atrophy to some extent. Together, these data show that neuroprotection can improve disease onset, but clearly provide evidence that one can uncouple MN survival from whole-animal survival and point to the neuromuscular junction perturbation as a primary event of ALS onset.

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“…A transgenic mouse model carrying the SOD1-G93A transgene was generated. Indeed, the mice developed ALS, exhibiting progressive motor deficits, paralysis, neurodegeneration, along with prominent mitochondrial abnormalities and increased ROS production in the spinal cord and brain [27,28]. Proteomic analysis of tissue samples identified that the SOD1 protein was carbonylated and aggregated in the spinal cord [29].…”

Section: Cell Models Of P53 For Ros Studymentioning

confidence: 99%

Models of reactive oxygen species in cancer

Ogasawara

Huang

2007

Drug Discovery Today: Disease Models

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Increased generation of reactive oxygen species (ROS) has been observed in cancer, degenerative diseases, and other pathological conditions. ROS can stimulate cell proliferation, promote genetic instability, and induce adaptive responses that enable cancer cells to maintain their malignant phenotypes. However, when cellular redox balance is severely disturbed, high levels of ROS may cause various damages leading to cell death. The studies of ROS effects on biological systems, their underlying mechanisms and therapeutic implications largely depend on proper experimental models. Here we review several in vitro and in vivo models for ROS research.

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Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis

Cited by 152 publications

References 31 publications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Sodium Valproate Exerts Neuroprotective EffectsIn Vivothrough CREB-Binding Protein-Dependent Mechanisms But Does Not Improve Survival in an Amyotrophic Lateral Sclerosis Mouse Model

Models of reactive oxygen species in cancer

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