ライフサイエンスコーパス: SOD1

1 and the antioxidant superoxide dismutase 1 (SOD1).

2 llo-enzyme copper-zinc superoxide dismutase (SOD1).

3 own for mutations in superoxide dismutase-1 (SOD1).

4 familial amyotrophic lateral sclerosis (fALS/SOD1).

5 protein (TDP-43) and superoxide dismutase 1 (SOD1).

6 phic lateral sclerosis-linked aggregation of SOD1.

7 omes of the mitochondrial pools of misfolded SOD1.

8 affected by disease had the most aggregated SOD1.

9 nonnative disulfide-cross-linked aggregated SOD1.

10 bit C. albicans SOD5 but not mammalian Cu,Zn-SOD1.

11 ion promotes high-affinity Zn(II) binding in SOD1.

12 e of astrocytes expressing ALS-linked mutant SOD1.

13 of hCCS available to interact with immature SOD1.

14 both Cu delivery and disulfide formation in SOD1.

15 ating the specific accumulation of misfolded SOD1.

16 ch lower affinity for copper than does Cu,Zn-SOD1.

17 the conserved intrasubunit disulfide bond in SOD1.

18 pulation of ErbB2 cancer cells show elevated SOD1.

19 sociated virus encoding a microRNA targeting SOD1.

20 n net charge upon single ET (e.g., DeltaZ(ET(SOD1)) =0.05+/-0.08 per electron, compared to DeltaZ(ET(

21 Quantitative RT-PCR of polg2, fis1, opa1, sod1/2 and bcl2a from isolated retina showed expression

22 n in PGC-1alpha, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression.

23 ture in a peptide model of the C-terminus of SOD1, a sequence that might serve as a potential source

24 ated protein variant superoxide dismutase 1 (SOD1)-A4V, whereas HSPA1L enhanced its aggregation.

25 crucial for the HSPA1A-mediated reduction in SOD1-A4V aggregation.

26 formed dimers and oligomers, but only mutant Sod1 accumulated in intracellular inclusions.

27 erone for Cu-zinc (Zn) superoxide dismutase (SOD1) activates by directly promoting both Cu delivery a

28 n copper chaperone for SOD1 (hCCS)-catalysed SOD1 activation based on crystal structures of reaction

29 nctional chaperoning role(s) for CCS1 during SOD1 activation.

30 from CCS1 to the entry site and then to the SOD1 active site by a thermodynamically driven affinity

31 d, where concomitant increases in copper and SOD1 activity are also evident.

32 scence change and added a parallel screen of SOD1 activity as a potential proxy for compound toxicity

33 ggest a previously unknown interplay between SOD1 acylation, metabolic regulation, and SOD1-mediated

34 other amyloidogenic proteins also inhibited SOD1 aggregation at low micromolar concentrations, where

35 se model of ALS impairs autophagy, increases SOD1 aggregation, and accelerates early disease onset wi

36 and aberrant dynamics, promoting neurotoxic SOD1 aggregation.

37 ngevity, and oxidative stress-induced mutant Sod1 aggregation.

38 (SC) transcriptomes reported from TDP-43 and SOD1 ALS mice and ALS patients with those from SCA2 mice

39 es annotated pathways shared with TDP-43 and SOD1 ALS mice and ALS patients.

40 genes occurs in C9 and sporadic ALS but not SOD1-ALS.

41 t ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time.

42 We examined wild-type SOD1 and six disease-related point mutants by using tand

43 entially binds a completely immature form of SOD1 and that the SOD1.CCS1 interaction promotes high-af

44 Importantly, secretion of wild-type human SOD1 and the ALS-linked mutant in human cells also requi

45 opose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology of ALS.

46 essing a Cu-containing superoxide dismutase (SOD1) and inducing Mn-containing SOD3 as a non-Cu altern

47 ction, and disturbed superoxide dismutase 1 (SOD1) and Keap1/Nrf2 antioxidant responses constitute im

48 To eliminate the contribution of endogenous Sod1, and better evaluate the effect of ALS-associated m

49 Heterozygous variants in SOD1 are a common cause of familial amyotrophic lateral

50 in the gene encoding superoxide dismutase 1 (SOD1) are the second most common cause of familial ALS,

51 y folded variants of superoxide dismutase 1 (SOD1) are thought to contribute to the pathogenesis of f

52 These results identify SOD1 as an ideal target for cancer therapy as SOD1 inhib

53 ges in the catalytic activity of immobilized SOD1 as well as its release from the s-MNPs/SOD1 polyion

54 model showed a significant reduction in CSF SOD1 at visit 6 (p < 0.001) with a mean reduction of 13.

55 restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the interactomes

56 n excitation-dependent decrease in misfolded SOD1 burden and autophagy overload.

57 e show that quinary interactions destabilize SOD1 by a similar energetic offset for most of the mutan

58 Molecular recognition of immature SOD1 by hCCS is driven by several interface interactions

59 onding to the Loop VII-beta8 sequence at the SOD1 C terminus was uniquely sensitive to denaturant.

60 We found that unlike mammalian Cu,Zn-SOD1, C. albicans SOD5 indeed rapidly loses its copper t

61 Based on these results, we suggest that SOD1 carries a housekeeping function that maintains ROS

62 Mutations in superoxide dismutase 1 (SOD1) cause 15-20% of familial amyotrophic lateral scler

63 Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neuro

64 Mutations in Cu-Zn superoxide dismutase 1 (SOD1) cause familial forms of amyotrophic lateral sclero

65 ct interaction with the copper chaperone for SOD1 (CCS).

66 ompletely immature form of SOD1 and that the SOD1.CCS1 interaction promotes high-affinity Zn(II) bind

67 CCS1 delivers Cu(I) to an entry site at the SOD1.CCS1 interface upon binding.

68 Activated mutant SOD1 CD8(+) T cells produce interferon-gamma, which elic

69 om baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85.

70 ay 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the p

71 n adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentrati

72 racted with either AMF7-63 or B8H10-reactive SOD1 conformers as well as a high proportion of interact

73 t SOD1 mice with higher amounts of misfolded SOD1 detected within the spinal cord.

74 Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate misfolded SOD1 ont

75 trajectory that Cu/Zn superoxide dismutase (SOD1) dimers take over the unfolding and dissociation fr

76 At longer exposures (25 min) the s-MNPs/SOD1 dispersion destabilizes.

77 on the structural plasticity of the immature SOD1 disulphide sub-loop, a characteristic which contrib

78 Complexation specifically stabilises the SOD1 disulphide sub-loop, priming it and the active site

79 otor neurons from patients with mutations in SOD1 exhibited dramatically different signatures.

80 d in the SOD1(G93A) rat model that misfolded SOD1 exists as distinct conformers and forms deposits on

81 cell coculture systems, we found that mutant SOD1-expressing CD8(+) T lymphocytes selectively kill mo

82 orm factor)), when compared to wild-type dog SOD1-expressing cells.

83 evaluate the effect of ALS-associated mutant Sod1 expression, we expressed human Sod1 WT and mutants

84 ermined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmen

85 G93A) ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundan

86 perty of each bead and that bead's effect on SOD1 fibrillization rate was with regard to bead mass.

87 over a time course of 42 days, during which SOD1 fibrils form, we detect the disappearance of the na

88 ndicate that MIF plays a significant role in SOD1 folding and misfolding mechanisms and strengthen th

89 which provide an extended surface upon which SOD1 folds.

90 We showed that both WT and mutant Sod1 formed dimers and oligomers, but only mutant Sod1 a

91 LR01 inhibited the aggregation of all tested SOD1 forms in vitro Next, we examined whether CLR01 coul

92 pper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae The

93 ctor, and we determined that exposure of the SOD1 functional loops facilitates this interaction.

94 sed SOL and sternomastoid (STM) muscles from SOD1(G37R) mice and performed Ca(2+)-imaging to monitor

95 SOD1(G37R) mice expressing a conditional allele of an AL

96 a phagocytic phenotype on denervated NMJs in SOD1(G37R) mice.

97 ease-resistant NMJs [soleus muscle (SOL)] in SOD1(G37R) mice.

98 ll types in ALS, we made use of a Drosophila Sod1 (G85R) knock-in model, in which all cells harbor th

99 Sod1(G86R) and Fezf2 knockout mouse lines were crossed t

100 n Amyotrophic Lateral Sclerosis mouse model, SOD1 G93A.

101 dependent interaction between motoneuron and SOD1 (G93A) CD8(+) T cells.

102 c/glycinergic inputs to E17.5 fetal MNs from SOD1(G93A) (SOD) mice in parallel with chloride homeosta

103 In a rat ALS model (SOD1(G93A) ) we previously demonstrated that spinal resp

104 EVs from brains and spinal cords of the SOD1(G93A) ALS mouse model, as well as from human SOD1 f

105 ree factors markedly extends survival in the SOD1(G93A) ALS mouse model, providing evidence for glios

106 Furthermore, mutant SOD1(G93A) and loxSOD1(G37R) mice injected with AAV2/9-M

107 overexpress MIF in the spinal cord of mutant SOD1(G93A) and loxSOD1(G37R) mice.

108 tal models of autoimmune encephalomyelitis-, SOD1(G93A) and rotenone models, mimicking these CNS dise

109 Further, the introduction of SOD1(G93A) and TDP43(A315T), established ALS-related mut

110 ent metabolite changes observed with the two SOD1(G93A) cell types highlight the role of the astrocyt

111 onal regeneration of motor neurons harboring SOD1(G93A) is impaired, but amenable for pharmacological

112 mir-17~92/nuclear PTEN axis in degenerating SOD1(G93A) LMC-MNs was confirmed in a double-transgenic

113 euronal suppression of NF-kappaB activity in SOD1(G93A) mice also resulted in neuroprotection with re

114 markedly reduced compared to presymptomatic SOD1(G93A) mice and wild types.

115 molyn sodium provides neuroprotection in the SOD1(G93A) mice by decreasing the inflammatory response.

116 Although the ALS-like phenotype of SOD1(G93A) mice is instigated by expression of the mutan

117 ous proteins implicated in ALS, and EVs from SOD1(G93A) mice were significantly depleted in myelin-ol

118 ssed the regenerative capability of axons in SOD1(G93A) mice with and without treatment with Y-27632.

119 yso-PC were also found in the spinal cord of SOD1(G93A) mice, a model of ALS.

120 n- and spinal cord-derived EVs, from NTg and SOD1(G93A) mice, are positive for the astrocyte marker G

121 In symptomatic SOD1(G93A) mice, axonal regeneration was markedly reduce

122 did not increase the lifespan of symptomatic SOD1(G93A) mice, but did improve axonal (re)innervation

123 hway has been shown to be neuroprotective in SOD1(G93A) mice, the most commonly used animal model of

124 nducible EphA4 KO at different timepoints in SOD1(G93A) mice, we found no benefits on motor function

125 sciatic nerve crush in pre- and symptomatic SOD1(G93A) mice.

126 n the tibialis anterior muscle of transgenic SOD1(G93A) mice.

127 stant to excitability changes in age-matched SOD1(G93A) mice.

128 terior muscle in cromolyn treated transgenic SOD1(G93A) mice.

129 nuclear PTEN in spinal MNs of presymptomatic SOD1(G93A) mice.

130 uromuscular function and extends survival in SOD1(G93A) mice.

131 7~92 improves motor deficits and survival in SOD1(G93A) mice.

132 microglia were toxic to motor neurons in the SOD1(G93A) mice.

133 rol synthesis occurred in the spinal cord of SOD1(G93A) mice; levels of sterol regulatory element bin

134 l mice to test for protective effects in the SOD1(G93A) model of ALS.

135 t proprioceptive neurons in the well-studied SOD1(G93A) mouse model for neurodegenerative motor neuro

136 oss of TBK1 function in motor neurons of the SOD1(G93A) mouse model of ALS impairs autophagy, increas

137 flammatory effects of cromolyn sodium in the SOD1(G93A) mouse model of ALS.

138 espread EphA4 reduction is beneficial in the SOD1(G93A) mouse model of ALS.

139 ere studied during the disease course in the SOD1(G93A) mouse model.

140 In the SOD1(G93A) mouse, FRZB was upregulated in the early stag

141 and the clinical presentation of ALS in the SOD1(G93A) mouse.

142 oceptive sensory neurons in the well-studied SOD1(G93A) mouse.

143 We previously demonstrated in the SOD1(G93A) rat model that misfolded SOD1 exists as disti

144 Here, using SOD1(G93A) rats and conformation-restricted antibodies s

145 nd astrogliosis in the lumbar spinal cord of SOD1(G93A) transgenic mice before the onset of symptoms,

146 g the ALS-associated superoxide dismutase-1 (SOD1)(G93A) mutant decreased spinal motoneuron loss.

147 s (ALS) mouse model, superoxide dismutase 1 (SOD1)(G93A), revealed that these EVs contain canonical e

148 Starting from about 4 postnatal weeks, SOD1-G93A and wild-type (WT) mice were evaluated in the

149 st extension of lifespan relative to control SOD1-G93A cohort.

150 ional and anatomical changes taking place in SOD1-G93A mice and their time course were investigated d

151 Notably, the functional sparing in SOD1-G93A mice at 12 weeks was paralleled by a marked ~5

152 red to age-matched WT controls, 12 weeks-old SOD1-G93A mice exhibited relatively mild or no motor imp

153 and phagocytotic pathways in presymptomatic SOD1-G93A mice expressing IL-10 + M3 or IL-10 alone.

154 eurons which remained virtually unchanged in SOD1-G93A mice surviving up to 19 weeks.

155 eptor can modulate inflammatory processes in SOD1-G93A mice, modestly delaying the age to paralysis.

156 vents take place in surviving motoneurons of SOD1-G93A mice, which sustain motor performance, and who

157 Plastic changes have been reported in the SOD1-G93A mouse model of amyotrophic lateral sclerosis,

158 flammatory cytokine, extends lifespan in the SOD1-G93A mouse model of familial ALS.

159 model that expresses a mutant of the murine Sod1 gene ubiquitously, a condition sufficient to induce

160 ing mutations in the superoxide dismutase 1 (SOD1) gene.

161 NA expression for the antioxidative enzymes, SOD1, GPx1 and HO-1, was reduced in aged M(1) receptor-d

162 of the gene encoding superoxide dismutase 1 (SOD1) have been linked to toxic protein aggregation in t

163 Mutations in Cu/Zn superoxide dismutase (Sod1) have been reported in both familial and sporadic a

164 nal mechanisms of human copper chaperone for SOD1 (hCCS)-catalysed SOD1 activation based on crystal s

165 al aging, we concluded that cells expressing Sod1 heterodimers showed decreased antioxidant activity,

166 2) and Wnt (MMTV-Wnt) transgenic mice to the SOD1 heterozygote or knockout mice.

167 e of a model enzyme, superoxide dismutase 1 (SOD1) immobilized by polyion coupling on dispersed MNPs

168 Levels of SOD1 in cerebrospinal fluid were transiently and only sl

169 tiated this study to investigate the role of SOD1 in mammary gland tumorigenesis as well as in normal

170 ignificantly prolonged circulation of active SOD1 in the blood stream compared to free SOD1 or SC nan

171 R01 could prevent the formation of misfolded SOD1 in the G93A-SOD1 mouse model of ALS and whether suc

172 CLR01 treatment decreased misfolded SOD1 in the spinal cord significantly.

173 We also found that the levels of aggregated SOD1 in the spinal cord were inversely correlated with t

174 ice accumulated reduced amounts of misfolded SOD1 in their spinal cords, with no observed effect on g

175 s that MIF acts as a chaperone for misfolded SOD1 in vivo and may have further implications regarding

176 cytotoxic segment of superoxide dismutase 1 (SOD1) in its oligomeric state.

177 ALS related protein superoxide dismutase I (SOD1) in mammalian cells, we show that quinary interacti

178 eta (Abeta), tau and superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of healthy individuals,

179 ALS mutant SOD1 induced reductions in Miro1 levels were Parkin depe

180 OD1 as an ideal target for cancer therapy as SOD1 inhibitors hold the potential to prevent the growth

181 ese results provide evidence that ALS mutant SOD1 inhibits axonal transport of mitochondria by induci

182 NF receptor-associated factor 6 (TRAF6) as a SOD1 interactor, and we determined that exposure of the

183 To test this hypothesis, here we dissected SOD1 into a set of peptides end-labeled with FRET probes

184 (DeltaPsim) and metabolic plasticity in the SOD1-iPSC derived myotubes.

185 In the same cells, decrease in SOD1 is associated with an elevation in both apoptosis a

186 This total regulation of net charge by SOD1 is attributed to the protonation of the bridging hi

187 hat translational incorporation of BMAA into SOD1 is directly responsible for its toxicity in neurode

188 ithelial cells are enriched in SOD1, whether SOD1 is essential for normal mammary gland development h

189 Our results show that SOD1 is essential for oncogene-driven proliferation, but

190 We now report that secreted SOD1 is functionally active and accompanied by export of

191 D1 mouse model of familial ALS, since mutant SOD1 is known to accumulate in the IMS of neural tissue

192 We previously reported that the dismutase SOD1 is overexpressed in breast cancer.

193 idue substitution in superoxide dismutase 1 (SOD1) is associated with canine degenerative myelopathy:

194 Superoxide dismutase 1 (SOD1) is the principal cytoplasmic superoxide dismutase

195 e, we show that Cu, Zn superoxide dismutase (SOD1) is unique among proteins in its ability to resist

196 Using Sod1-KD cells we found that the WT-A4V heteromers formed

197 uman cells knocked down for endogenous Sod1 (Sod1-KD), and in sod1Delta yeast cells.

198 ion of mir-17~92 significantly rescues human SOD1(+/L144F) MNs, and intrathecal delivery of adeno-ass

199 stem cell system and recapitulated in human SOD1(+/L144F)-induced pluripotent stem cell (iPSC)-deriv

200 neuroprotection with reduction of misfolded SOD1 levels and significant extension of life span.

201 us phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutation

202 In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy

203 y investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients

204 screen in a Caenorhabditis elegans model of SOD1-linked ALS identified the USP7 ortholog as a suppre

205 ion and is a candidate therapeutic target in SOD1-linked ALS.

206 In this way, hCCS-catalysed SOD1 maturation is finessed to minimise copper wastage a

207 Superoxide dismutase-1 (SOD1) maturation comprises a string of posttranslational

208 hese findings suggest that soluble misfolded SOD1 may be the disease driver in ALS, whereas aggregate

209 mt), we suggest that the dismutases SOD2 and SOD1 may play key roles in the establishment of the mito

210 neurodegeneration, and BMAA modification of SOD1 may serve as a biomarker of ALS.

211 he disease driver in ALS, whereas aggregated SOD1 may serve to sequester the toxic species acting in

212 responding levels in untreated patients with SOD1-mediated ALS and in healthy controls.

213 RNA can be used as a potential treatment for SOD1-mediated ALS.

214 en SOD1 acylation, metabolic regulation, and SOD1-mediated cell survival.

215 s the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis.

216 as well as shortened the lifespan of mutant SOD1 mice with higher amounts of misfolded SOD1 detected

217 ate disease onset but extend the lifespan of SOD1 mice.

218 l debris phagocytosis, on NMJ denervation in SOD1 mice.

219 e results demonstrate that CLR01 can inhibit SOD1 misfolding and aggregation both in vitro and in viv

220 r (MIF) was shown to directly inhibit mutant SOD1 misfolding and binding to intracellular membranes.

221 the formation of misfolded SOD1 in the G93A-SOD1 mouse model of ALS and whether such inhibition woul

222 s, we investigated the IMS-UPRmt in the G93A-SOD1 mouse model of familial ALS, since mutant SOD1 is k

223 he lifespan of most popular high copy number SOD1 mutant mice might be too short to acknowledge benef

224 asurements were obtained in a cohort of G93A SOD1 mutant overexpressing rats and compared with contro

225 sis (ALS)-associated superoxide dismutase 1 (SOD1) mutant protein induces changes in HSP70 and HSC70

226 with disease progression in spinal cord from SOD1-mutant mouse models, and reductions in membralin/EA

227 These results show that the hG93A SOD1 mutation causes metabolic and ultrastructural cellu

228 essing a conditional allele of an ALS-linked SOD1 mutation were crossed with Tph2-Cre mice expressing

229 rebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sc

230 addition, we also found that ALS-associated Sod1 mutations reduced nuclear localization and, consequ

231 In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the

232 S, including those caused by TDP-43, VCP and SOD1 mutations, supporting the concept that multiple ALS

233 valuating tofersen in adults with ALS due to SOD1 mutations.

234 tic intervention in the dozens of ALS-linked SOD1 mutations.

235 ent in patients with ALS caused by different SOD1 mutations.

236 s SOD1 levels in leukocytes in patients with SOD1 mutations.

237 f amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.

238 Although proliferative, SOD1 myoblasts demonstrated delayed and reduced fusion e

239 Additionally, SOD1 myotubes exhibited significantly reduced length and

240 Also, SOD1 myotubes had loosely arranged myosin heavy chain an

241 y reduced contractile force and synchrony in SOD1 myotubes.

242 ses, we replicated known ALS genes including SOD1, NEK1 and FUS.

243 npoints risk regions of ALS genes, including SOD1, NEK1, TARDBP, and FUS While not clearly implicatin

244 lated to a constellation of mitochondria-ROS-SOD1/Nrf2 changes in the placenta.

245 1 develop paralysis and accumulate misfolded SOD1 onto the cytoplasmic faces of intracellular organel

246 ive action has not been tested previously on SOD1 or in the context of ALS.

247 ve SOD1 in the blood stream compared to free SOD1 or SC nanozymes (half-life was 60 vs 6min).

248 Astrocytes isolated from mutant human SOD1-overexpressing mice induce motor neuron death in co

249 However, whether SOD1 plays an active role in tumor formation in vivo has

250 SOD1 as well as its release from the s-MNPs/SOD1 polyion complex upon application of the ELF MF for

251 ophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron diseas

252 ould recapitulate features of human ALS (ie, SOD1 protein aggregation, reduced cell viability, pertur

253 ular phenotype of dogs expressing the mutant SOD1 protein and reveals that species-specific sequence

254 oducing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by diff

255 nimals involves an increase in mature mutant SOD1 protein in the disease-affected spinal cord, where

256 e dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis.

257 known to increase the susceptibility of the SOD1 protein to form insoluble intracellular aggregates.

258 ic combinations of wild-type (WT) and mutant Sod1 proteins A4V, L38V, G93A, and G93C in human cells.

259 e was a high soluble misfolded/soluble total SOD1 ratio.

260 blood and muscle with increasing severity), SOD1 (reductions in muscle and increases in blood with i

261 s of function is the underlying mechanism in SOD1-related motor neuron disease and should be consider

262 lta/Delta mutation, demonstrating a role for SOD1 repression by Mac1p in preserving respiration.

263 te that substituting any serine with BMAA in SOD1 results in structural destabilization and aberrant

264 residue pK(a) 's upon ET at copper, allowing SOD1's "electrostatic loop" to attract superoxide with e

265 sulting amino acid substitutions destabilize SOD1's protein structure, leading to its self-assembly i

266 ession of mutant Cu/Zn-superoxide dismutase (SOD1) selectively affects motor neurons in the central n

267 ed before application of previously proposed SOD1 silencing as a treatment option for amyotrophic lat

268 s in human cells knocked down for endogenous Sod1 (Sod1-KD), and in sod1Delta yeast cells.

269 pression of oxidative stress response genes, Sod1, Sod2 and others.

270 elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defenc

271 e and reduce production of potentially toxic SOD1 species.

272 of intermediates in the folding of monomeric SOD1 suggests that the unfolded ensemble is a potential

273 ic mutations linked to ALS (eg, mutations in SOD1, TARDBP, and C9orf72) enhance this neuroinflammatio

274 uncating variant c.335dupG (p.C112Wfs*11) in SOD1 that leads to total absence of enzyme activity.

275 Mac1p downregulates the major Cu consumer SOD1 to spare Cu for respiration that is essential for v

276 he NES consensus sequence relocalizes mutant SOD1 to the nucleus, resulting in higher toxicity in cel

277 iPSC-derived muscle model that demonstrates SOD1 toxicity effects on human muscle regeneration, cont

278 c activity and ability to retain and protect SOD1 under physiological conditions.

279 S-linked protein Cu,Zn superoxide dismutase (SOD1) upon translation promotes protein misfolding and a

280 ential inhibitors of superoxide dismutase 1 (SOD1) using ThT-fluorescence including the different pha

281 r, we hypothesized that an equivalent equine SOD1 variant would share similar perturbations in vitro,

282 ted in cells expressing the equivalent horse SOD1 variant.

283 pher the relationships between the different SOD1 variants (aggregated, soluble misfolded, soluble to

284 change was not universally fulfilled by all SOD1 variants and differentiated TRAF6 interacting from

285 ed polyubiquitination and aggregation of the SOD1 variants are independent events.

286 For six of the seven SOD1 variants, increasing activation prompted dimers to

287 itination and aggregation of the interacting SOD1 variants.

288 TRAF6 interacting from TRAF6 noninteracting SOD1 variants.

289 As in human ALS, expression of mutant dog SOD1 was associated with statistically significant incre

290 SOD1 was highly resistant to inhibition of its activity,

291 Using recombinant WT and mutant SOD1, we found that CLR01 inhibited the aggregation of a

292 ce is instigated by expression of the mutant SOD1, we show the improved phenotype of the Cu(II)(atsm)

293 in the gene encoding superoxide dismutase 1 (SOD1) were treated with a single intrathecal infusion of

294 rmal breast epithelial cells are enriched in SOD1, whether SOD1 is essential for normal mammary gland

295 aggregation of human superoxide dismutase 1 (SOD1), which is known to form misfolded aggregates in pa

296 hSOD1 G93A that overexpresses human mutated SOD1, which is known to increase the susceptibility of t

297 Charge regulation by SOD1 would prevent long range coulombic perturbations to

298 sized that in vitro expression of mutant dog SOD1 would recapitulate features of human ALS (ie, SOD1

299 d mutant Sod1 expression, we expressed human Sod1 WT and mutants in human cells knocked down for endo

300 ound that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had n