Identification of a new missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD-1) gene in a family with amyotrophic lateral sclerosis

Elshafey, Alaa; Wg, Lanyon; Jm, Connor

doi:10.1093/hmg/3.2.363

Cited by 64 publications

(16 citation statements)

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“…14 Mutations in the gene for Cu,ZnSOD have been identified in familial amyotrophic lateral sclerosis (ALS), a disease characterized by damage and loss of neurons in both the brain and the spinal cord. 15 Transgenic mice overexpressing wide-type Cu,ZnSOD gene show resistance to SCI, indicating that Cu,ZnSOD has an important role in protecting against spinal neuron death. 16 NAD(P)H:quinone oxidoreductase 1 (NQO1) is another important antioxidant enzyme that has recently been demonstrated to has a protective role in electrophilic stress underlying spinal cord damage.…”

Section: Ros and Oxidative Stress In Scimentioning

confidence: 99%

Oxidative stress in spinal cord injury and antioxidant-based intervention

Jia

Zhu

Li³

et al. 2011

Spinal Cord

259

176

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Study design: Literature review. Objectives: Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI. Methods: PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article. Results: Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds. Conclusion: ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.

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Section: Ros and Oxidative Stress In Scimentioning

confidence: 99%

Oxidative stress in spinal cord injury and antioxidant-based intervention

Jia

Zhu

Li³

et al. 2011

Spinal Cord

259

176

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“…Furthermore, of the 72 amino acids within SOD1 that are mutated in FALS, 88% (63 out of 72) are conserved in zebrafish, compared with 90% (65 out of 72) in the mouse and 72% (52 out of 72) in the fly. We mutated Sod1 by changing glycine 93 to arginine (G93R); this mutation affects a conserved amino acid that is often mutated in FALS (http://alsod.iop.kcl.ac.uk) (Elshafey et al, 1994).…”

Section: Generation Of Transgenic Sod1 Zebrafishmentioning

confidence: 99%

“…Mutations in the superoxide dismutase (SOD1) gene account for 20% of FALS cases Rosen et al, 1993;Valdmanis and Rouleau, 2008). To date, over 150 mutations in SOD1 have been discovered, including the point mutation G93R (Elshafey et al, 1994;Turner and Talbot, 2008).…”

Section: Introductionmentioning

confidence: 99%

A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease

Ramesh

Lyon²,

Pineda³

et al. 2010

Disease Models &Amp; Mechanisms

135

128

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SUMMARYAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that, for ~80% of patients, is fatal within five years of diagnosis. To better understand ALS, animal models have been essential; however, only rodent models of ALS exhibit the major hallmarks of the disease. Here, we report the generation of transgenic zebrafish overexpressing mutant Sod1. The construct used to generate these lines contained the zebrafish sod1 gene and ~16 kb of flanking sequences. We generated lines expressing the G93R mutation, as well as lines expressing wild-type Sod1. Focusing on two G93R lines, we found that they displayed the major phenotypes of ALS. Changes at the neuromuscular junction were observed at larval and adult stages. In adulthood the G93R mutants exhibited decreased endurance in a swim tunnel test. An analysis of muscle revealed normal muscle force, however, at the end stage the fish exhibited motoneuron loss, muscle atrophy, paralysis and premature death. These phenotypes were more severe in lines expressing higher levels of mutant Sod1 and were absent in lines overexpressing wild-type Sod1. Thus, we have generated a vertebrate model of ALS to complement existing mammal models.

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“…More than 50 SOD1 mutations have now been identified. Approximately one-fourth of FALS cases carry SOD1 mutations (Siddique et al, 1991;Aoki et al, 1993;Rosen et al, 1993;Elshafev et al, 1994;Nakano et al, 1994;Radunovic and Leigh, 1996;Cudkowicz et al, 1997).…”

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confidence: 99%

Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

Se²,

La³

et al. 1997

Journal of Neurochemistry

709

406

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Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2 '-deoxyguanosine (OH 8dG) levels were increased in SALS motor cortex but not in FALS patients. Malondialdehyde levels showed no significant changes. Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehydemodified protein, and OH8dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS.

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Identification of a new missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD-1) gene in a family with amyotrophic lateral sclerosis

Cited by 64 publications

References 0 publications

Oxidative stress in spinal cord injury and antioxidant-based intervention

Oxidative stress in spinal cord injury and antioxidant-based intervention

A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease

Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

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