Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis

Watanabe, Shohei; Nagano, Seiichi; Duce, James A.; Kiaei, Mahmoud; Li, Qiao Xin; Tucker, Stephanie C.; Tiwari, Ashutosh; Brown, Robert H.; Beal, M. Flint; Hayward, Lawrence J.; Culotta, Valeria C.; Yoshihara, Satoshi; Sakoda, Saburo; Bush, Ashley I.

doi:10.1016/j.freeradbiomed.2007.02.004

Cited by 49 publications

(39 citation statements)

References 48 publications

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“…The C111S mutation markedly attenuates the affinity for Cu and increases protein stability. This implies that the Cys111 residue is critical for the stability of mutant SOD1 (29). These hypothetical mechanisms may have influenced the different phenotypes in our patients.…”

Section: Discussionmentioning

confidence: 85%

Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Nakamura¹,

Hineno²,

Yoshida³

et al. 2012

Amyotrophic Lateral Sclerosis

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Objectives: To identify the disease-causing mutation in and report on the clinical features of a Japanese family that had coexisting phenotypes of amyotrophic lateral sclerosis and spinal muscular atrophy. Methods: The family comprised 9 patients (6 men and 3 women). We reviewed their clinical records and performed mutation analysis of the copper/zinc superoxide dismutase (SOD1) gene in some of these patients. Results:The patients either had a rapid (n = 7) or an extremely long (n = 2) clinical course. The mean age at onset was 39.0 ± 13.7 years (range: 20-68 years). The initial symptoms were bulbar palsy (n = 2), upper (n = 4) or lower (n = 2) limb muscle weakness, or leg cramps (n = 1). The total disease duration varied widely, ranging from 1 year to >69 years. We identified a SOD1 C111Y mutation in the patients of this family. Conclusion: The family showed a marked intrafamilial phenotypic variation associated with the SOD1 C111Y mutation. Elucidating the biological basis of disease expression in patients with SOD1 C111Y mutation may provide us with useful information to develop therapeutic approaches and to prevent disease progression.

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Section: Discussionmentioning

confidence: 85%

Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Nakamura¹,

Hineno²,

Yoshida³

et al. 2012

Amyotrophic Lateral Sclerosis

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“…Nevertheless, one report showed that Atp5d is copper sensitive (Chen et al, 2002) and a low concentration of mitochondrial copper can lead to its downregulation without altering the expression level of other subunits of the respiratory chain. This characteristic might affect Atp5d regulation in SOD1-related cases of ALS, in which altered affinity of mutant SOD1 for copper has been described (Watanabe et al, 2007). Atp5d has a crucial role in the ATP production process at the end of the mitochondrial respiratory chain.…”

Section: Discussionmentioning

confidence: 99%

Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS

Ferraiuolo¹,

Heath²,

Holden³

et al. 2007

J. Neurosci.

183

174

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The cellular pathways of motor neuronal injury have been investigated in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis (ALS) using laser-capture microdissection and microarray analysis. The advantages of this study include the following: analysis of changes specifically in motor neurons (MNs), while still detecting effects of interactions with neighboring cells; the ability to profile changes during disease progression, an approach not possible in human ALS; and the use of transgenic mice bred on a homogeneous genetic background, eliminating the confounding effects arising from a mixed genetic background. By using this rigorous approach, novel changes in key cellular pathways have been detected at both the presymptomatic and late stages,

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“…Cys-111, a potential site of palmitoylation, undergoes oxidation (23,50) and glutathionylation (48) and is thought to be important for copper binding (51), all processes implicated in the structural stability of SOD1. The reactivity of Cys-111 is not surprising given its location on the surface of the protein near the dimer interface.…”

Section: Discussionmentioning

confidence: 99%

Palmitoylation of Superoxide Dismutase 1 (SOD1) Is Increased for Familial Amyotrophic Lateral Sclerosis-linked SOD1 Mutants

Antinone

Ghadge

Lam

et al. 2013

Journal of Biological Chemistry

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Background: Mutations in SOD1 cause familial amyotrophic lateral sclerosis (ALS). Results: SOD1 undergoes palmitoylation in the spinal cord and multiple cell types. Palmitoylation occurs predominantly on immature SOD1 and is increased for ALS-linked SOD1 mutants. Conclusion: Palmitoylation is a reversible post-translational modification of SOD1 cysteine residues. Significance: Palmitoylation could affect SOD1 toxicity by altering its folding, membrane targeting, and/or function.

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Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis

Cited by 49 publications

References 48 publications

Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS

Palmitoylation of Superoxide Dismutase 1 (SOD1) Is Increased for Familial Amyotrophic Lateral Sclerosis-linked SOD1 Mutants

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