ライフサイエンスコーパス: SOD1

1 familial amyotrophic lateral sclerosis (fALS/SOD1).

2 linked forms of Cu, Zn superoxide dismutase (SOD1).

3 establish an updated natural history of ALS(SOD1).

4 in the gene encoding superoxide dismutase 1 (SOD1).

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

6 ry site" for copper ion delivery on immature Sod1.

7 ch is a stable and wild-type-like variant of SOD1.

8 mine to lower SOD1 levels in the CSF in fALS/SOD1.

9 gregation and cross-aggregation processes of SOD1.

10 sight to the CNS-selective effects of mutant SOD1.

11 ts, with no statistical significance between SOD1(A4V) and SOD1(non-A4V) (p=0.72, Kruskal-Wallis).

12 ease in ALS-forced vital capacity decline in SOD1(A4V) compared with SOD1(non-A4V) (p=0.02).

13 y significant increase in ALS-FRS decline in SOD1(A4V) compared with SOD1(non-A4V) participants (p=0.

14 SOD1(A4V) is an aggressive, but relatively homogeneous f

15 SOD1(A4V) survival probability (median survival 1.2 year

16 tients with the A4V (Ala-Val) SOD1 mutation (SOD1(A4V)), the largest mutation population in North Ame

17 l SOD1 was 4.6+/-6.0 and 1.4+/-0.7 years for SOD1(A4V).

18 t acyl-mimicking mutations at K122 decreased SOD1 accumulation in mitochondria, initially hinting tha

19 porting a novel copper-induced mechanism for Sod1 activation.

20 with concomitant release of copper into the Sod1 active site.

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

22 s activation is critical because the loss of SOD1 activity blocked spore germination at outgrowth.

23 creases in intracellular Cu((II)) levels and SOD1 activity.

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

25 Importantly, oxidatively damaged SOD1 aggregates have been observed in both familial and

26 urvival of injected mice was determined, and SOD1 aggregates in the facial nuclei were quantified dur

27 es, and the levels of sedimentable insoluble SOD1 aggregates were significantly higher in the spinal

28 that misfolded alpha-synuclein can increase SOD1 aggregation and suppose that alpha-synuclein seeds

29 finitively link cytotoxicity associated with SOD1 aggregation in ALS to a nonnative trimeric SOD1 spe

30 ence of partly unfolded intermediates in the SOD1 aggregation process and presents new clues to the m

31 ity, the key molecular properties related to SOD1 aggregation.

32 170 different mutations in the gene encoding SOD1 all cause amyotrophic lateral sclerosis (ALS).

33 t postnatal day 180 (P180), FF and S NMJs of SOD1 already showed, respectively, lower and higher quan

34 survival was also observed for a G93A mutant SOD1 ALS strain.

35 elivery of copper-zinc superoxide dismutase (SOD1), an efficient ROS scavenger, to the site of injury

36 which express a dismutase-inactive mutant of SOD1 and are considered a model of familial ALS.

37 r SOD1 (hCCS) forms a transient complex with SOD1 and catalyses the final stages of its maturation.

38 SOD1 and CCS formed a highly stable heterodimer in human

39 ts and was not observed in vitro unless both SOD1 and CCS were overexpressed.

40 rectly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membranes, but the

41 searchers have sought the connection between SOD1 and motor neuron death.

42 d TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively).

43 ures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell death.

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

45 antioxidant enzymes, superoxide dismutase 1 (SOD1) and peroxiredoxin-4 (PRDX4) during hyperosmotic st

46 cytoplasmic protein, superoxide dismutase 1 (SOD1), and its mutant form linked to amyotrophic lateral

47 destabilize the native dimeric structure of SOD1, and plaques containing misfolded and aggregated SO

48 te that cell-surface copper transporters and SOD1 are required for completion of the spore germinatio

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

50 ds do not take place locally but require the SOD1 barrel to unfold globally.

51 recognize misfolded SOD1, but not native wt SOD1 both in vitro and in vivo.

52 st the NES-like sequence recognize misfolded SOD1, but not native wt SOD1 both in vitro and in vivo.

53 Furthermore, stabilization of wild-type SOD1 by chemical modification including cisplatination,

54 hCCS mutation abrogates the interaction with SOD1 by inhibiting hCCS zinc binding.

55 s immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidatio

56 ozyme) for copper/Zinc superoxide dismutase (SOD1) by polyion condensation with a conventional block

57 ylation of K122 on SOD1, while not impacting SOD1 catalytic activity, suppressed the ability of SOD1

58 Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a fatal

59 evealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal

60 that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation.

61 Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturatio

62 The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, an

63 The DeltaGHet of each ALS variant SOD1 correlated with patient survival time after diagnos

64 of a self-aggregation process by additional SOD1 could not be confirmed in our models.

65 focused on the mechanisms underlying mutant SOD1 cytotoxicity.

66 , based on the testing in a rodent model the SOD1 DC nanozymes are promising modality for scavenging

67 lity to rescue cells from toxicity caused by SOD1 deletion.

68 OD1 in vivo and in vitro, whereas aggregated SOD1 did not exert any effect in both experimental setup

69 g apo-, Zn-, and Cu,Zn-superoxide dismutase (SOD1) dimers.

70 mediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper i

71 nt activation of the superoxide dismutase 1 (SOD1) during spore germination.

72 f ALS-linked SOD1 mutants and wild-type (wt) SOD1 exposes a normally buried nuclear export signal (NE

73 gated [Ca2+]c and Miro1 levels in ALS mutant SOD1 expressing neurons.

74 drial axonal transport deficit in ALS mutant SOD1-expressing cortical and motor neurons.

75 The CNS-specific impact of ubiquitous mutant SOD1 expression is recapitulated in transgenic mouse mod

76 Deleting mutant SOD1 expression selectively in brainstem serotonin neuro

77 showed that, in the absence of ERalpha, G93A-SOD1 failed to activate OMI and the proteasome, confirmi

78 ults demonstrate the IMS-UPRmt activation in SOD1 familial ALS, and suggest that sex differences in t

79 The effect of each acyl group on the rate of SOD1 fibril nucleation and elongation were quantified in

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

81 ates how the rate of superoxide dismutase-1 (SOD1) fibrillization is affected by 12 different beads w

82 The addition of ThT-negative, acylated SOD1 fibrils to organotypic spinal cord failed to produc

83 ly results from the addition of ThT-positive SOD1 fibrils.

84 r oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood.

85 understanding of ALS disease progression and SOD1 folding and stability, cytotoxic species and mechan

86 red in two nerve-muscle preparations of male SOD1(G37R) mice and their wild-type (WT) littermates: th

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

88 glial activation crossed with SOD1(G93A) and SOD1(G37R) mouse models, we discovered that the preonset

89 e this role, we bred MIF-deficient mice with SOD1(G85R) mice, which express a dismutase-inactive muta

90 rogression and shortened the lifespan of the SOD1(G85R) mutant mice.

91 clerosis-linked SOD1 mutants, SOD1(G93A) and SOD1(G85R) We utilized a computational algorithm for map

92 ds of SOD1(G85R)-MIF(-/-) mice than in their SOD1(G85R)-MIF(+/+) littermates.

93 significantly higher in the spinal cords of SOD1(G85R)-MIF(-/-) mice than in their SOD1(G85R)-MIF(+/

94 In SOD1(G86R) mice, an animal model of amyotrophic lateral

95 mitochondria in motor neurons isolated from SOD1 G93A transgenic mice and in ALS mutant SOD1 transfe

96 of a mutant form of superoxide dismutase 1 (SOD1 G93A) that causes astrocyte dysfunction and neurode

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

98 At disease end-stage in a rat ALS model (SOD1(G93A) ), acute intermittent hypoxia (AIH) restores

99 mutant form of human superoxide dismutase 1 (SOD1(G93A) ).

100 maging of microglial activation crossed with SOD1(G93A) and SOD1(G37R) mouse models, we discovered th

101 ophic lateral sclerosis-linked SOD1 mutants, SOD1(G93A) and SOD1(G85R) We utilized a computational al

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

103 lower extracellular lactate, those with only SOD1(G93A) astrocytes exhibited the reverse.

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

105 temporal precision and signal integration in SOD1(G93A) developing networks at the postsynaptic site.

106 however, lifespan was extended in Atg7 cKO; SOD1(G93A) double-mutant mice.

107 iving cells, and reduced the cytotoxicity of SOD1(G93A) expressed in motor neuron-like cells.

108 We observed increased glucose uptake with SOD1(G93A) expression in all co-cultures, but while co-c

109 detection of a longer persistence of GABA in SOD1(G93A) glycinergic terminals in cultured and ex vivo

110 Deletion of FGFBP1 from SOD1(G93A) mice also accelerates NMJ degeneration and de

111 High levels of PPIA were found in the CSF of SOD1(G93A) mice and rats and sporadic ALS patients, sugg

112 Early studies with the original transgenic SOD1(G93A) mice in the hybrid background (B6SJL-Tg(SOD1-

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

114 loit organotypic cultures from wild-type and SOD1(G93A) mice to investigate the development of glycin

115 during aging and before NMJ degeneration in SOD1(G93A) mice, a mouse model for amyotrophic lateral s

116 before NMJ degeneration during aging and in SOD1(G93A) mice, a mouse model for amyotrophic lateral s

117 the cerebral lateral ventricles of neonatal SOD1(G93A) mice, and impact on disease progression and s

118 In SOD1(G93A) mice, loss of HIPK2 delays disease onset, red

119 ads to a significant increase in survival in SOD1(G93A) mice.

120 toneuron cell death and extended survival of SOD1(G93A) mice.

121 ayed disease onset and increased survival of SOD1(G93A) mice.

122 for FGFBP1 at NMJs in developing, aging and SOD1(G93A) mice.

123 ainst Nogo-A showed a positive effect in the SOD1(G93A) mouse model of ALS, and a humanised form of t

124 uromuscular junction denervation in a mutant SOD1(G93A) mouse model of amyotrophic lateral sclerosis

125 d motor neurons and extended survival in the SOD1(G93A) mouse model of familial ALS by 11 d.

126 motor neurons, and extended survival in the SOD1(G93A) mouse model of familial ALS.

127 By crossing Atg7 cKO mice to the SOD1(G93A) mouse model, we found that autophagy inhibiti

128 vation by targeted reduction of gamma-MNs in SOD1(G93A) mutants delays symptom onset and prolongs lif

129 co-cultures, but while co-cultures with only SOD1(G93A) neurons had lower extracellular lactate, thos

130 lerate were observed in co-culture with only SOD1(G93A) neurons while glutamate was reduced in all co

131 for therapeutic efficacy in mice expressing SOD1(G93A) on a mixed genetic background.

132 citability, affecting motor outputs in early SOD1(G93A) pathogenesis.

133 r neuron numbers were decreased in end-stage SOD1(G93A) rats ( approximately 30% survival; p < 0.001)

134 In end-stage male SOD1(G93A) rats and wild-type littermates, we investigat

135 Mechanisms enhancing pLTF in end-stage SOD1(G93A) rats are not known.

136 n increased MN bursting activity in immature SOD1(G93A) spinal cords and by immunofluorescence micros

137 ction of alpha-synuclein and SOD1 seeds into SOD1(G93A) transgenic ALS mice.

138 ial cell proliferation in the spinal cord of SOD1(G93A) transgenic mice correlates with the expressio

139 We applied qMotor in SOD1(G93A) transgenic mice in an inbred C57BL/6J backgro

140 As an example, we apply qMotor to SOD1(G93A) transgenic mice.

141 Mutant superoxide dismutase 1 (SOD1(G93A)) expression in astrocytes is selectively toxi

142 LS expressing mutant superoxide dismutase 1 (SOD1(G93A)), we show that motor neurons form large autop

143 ER stress, induced by tunicamycin or SOD1(G93A), activates HIPK2 by phosphorylating highly co

144 te was reduced in all co-cultures expressing SOD1(G93A).

145 ain and spinal cord of superoxide dismutase (SOD1) G93A transgenic mice.

146 93A) mice in the hybrid background (B6SJL-Tg(SOD1-G93A) have been criticized because of high noise in

147 evelopment of ALS, with the mutations in the SOD1 gene being an additional factor.

148 h more than 150 ALS-related mutations in the SOD1 gene.

149 sed by a mutation in Sod1) with ASOs against Sod1 has been shown to substantially slow disease progre

150 f lysine residues in superoxide dismutase-1 (SOD1) has been previously shown to decrease its rate of

151 plaques containing misfolded and aggregated SOD1 have been found in the motor neurons of patients wi

152 The copper chaperone for SOD1 (hCCS) forms a transient complex with SOD1 and cata

153 on, structure and disassociation of the hCCS-SOD1 heterodimer.

154 he interface may drastically destabilize the SOD1 homodimer, with several modifications exhibiting a

155 The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 2

156 d mutations in Cu/Zn superoxide dismutase 1 (SOD1) impair axonal transport of mitochondria in motor n

157 cyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from A

158 ssing or boosting respiration levels toggled SOD1 in or out of the mitochondria, respectively.

159 as cytotoxicity of the ALS-linked mutants of SOD1 in primary motor neurons and in a Danio rerio (zebr

160 ock the prion-like propagation of oligomeric SOD1 in spinal cord.

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

162 echanism against proteotoxicity of misfolded SOD1 in the nucleus.

163 toplasmic versus the secreted form of mutant SOD1 in the pathology of ALS.

164 ibrils increased the oligomerization rate of SOD1 in vivo and in vitro, whereas aggregated SOD1 did n

165 lation might alter the prion-like seeding of SOD1 in vivo has not been addressed.

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

167 rganotypic spinal cord failed to produce the SOD1 inclusion pathology that typically results from the

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

169 on of misfolded SOD1 and rescued from mutant SOD1-induced cell death.

170 otential implications of oxidative stress in SOD1-induced cytotoxicity remain elusive.

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

172 oligomers of mutant superoxide dismutase 1 (SOD1) into the cytoplasm of invertebrate neurons rapidly

173 copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond.

174 show that a respiration-defective mutant of SOD1 is also impaired in its ability to rescue cells fro

175 Our data indicate that SOD1 is directly or indirectly involved in ALS oligodend

176 s-linked multilayer polyion complex in which SOD1 is first incorporated into a polyion complex with p

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

178 Sod1 is the predominant disulfide bond-requiring enzyme

179 ound that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyo

180 We found that the accumulation of misfolded SOD1, its association with mitochondrial and ER membrane

181 ntravenous injection of DC nanozymes (5kU of SOD1/kg) improved the recovery of locomotor functions in

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

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

184 afety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1.

185 SOD1 levels were measured in erythrocytes and CSF.

186 These results suggest that, in SOD1-linked ALS mice, symptoms are a product of abnormal

187 s a novel therapeutic strategy, not only for SOD1-linked ALS, but possibly also for sporadic ALS.

188 a plausible strategy for prolonging life in SOD1-linked ALS.

189 mt could be specifically initiated by mutant SOD1 localized in the IMS.

190 Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer forma

191 n may play an important role in CCS-mediated SOD1 maturation.

192 tion in mitochondria, initially hinting that SOD1 may inhibit respiration directly within the interme

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

194 ls, we discovered that the preonset phase of SOD1-mediated disease is characterized by development of

195 These findings place SOD1-mediated inhibition of respiration upstream of its

196 In the MC4R null background, G93A SOD1 mice become markedly hypometabolic, overweight and

197 e spinal cords of female, but not male, G93A-SOD1 mice showed elevation of OMI and proteasome activit

198 me characteristic changes observed in mutant SOD1 mice.

199 ssion of superoxide dismutase 1 (SOD1) or an SOD1 mimetic.

200 interface that becomes exposed upon mutated SOD1 misfolding and monomerization.

201 but the role of endogenous MIF in modulating SOD1 misfolding in vivo remains unknown.

202 ine the effects of oxidative modification on SOD1 monomer and homodimer stability, the key molecular

203 ntermediate for CCS monomers, and lowest for SOD1 monomers.

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

205 Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-b

206 o the longer lifespan of females in the G93A-SOD1 mouse.

207 bolism in the mutant superoxide dismutase 1 (SOD1) mouse model of ALS (G93A SOD1) would alter motor f

208 at, in vitro, mutant superoxide dismutase 1 (SOD1) mouse oligodendrocytes induce WT motor neuron (MN)

209 scued sympathetic, sensory, and motor wt and SOD1 mutant neurons from trophic factor withdrawal-induc

210 misfolded and toxic superoxide dismutase 1 (SOD1) mutant proteins may find application in attenuatin

211 reclinical stages of superoxide dismutase 1 (SOD1)-mutant-mediated disease.

212 whole, our results reveal a reversed MUSP in SOD1 mutants and highlight MU-specific synaptic changes

213 Here, we show that misfolding of ALS-linked SOD1 mutants and wild-type (wt) SOD1 exposes a normally

214 Our data suggest that SOD1 mutants are removed from the nucleus by CRM1 as a d

215 We show that SOD1 mutants designed to promote trimerization increase

216 d that S-acylation increased for ALS-causing SOD1 mutants relative to wild type.

217 1M displayed high binding specificity toward SOD1 mutants, inhibited their amyloid aggregation in vit

218 amilial amyotrophic lateral sclerosis-linked SOD1 mutants, SOD1(G93A) and SOD1(G85R) We utilized a co

219 Patients with the A4V (Ala-Val) SOD1 mutation (SOD1(A4V)), the largest mutation populati

220 e progression, were distinguished from other SOD1 mutation patients (SOD1(non-A4V)) for analysis.

221 ddress this, we generated mice with the G93A SOD1 mutation that also lacked the melanocortin-4 recept

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

223 cted and -unaffected dogs homozygous for the SOD1 mutation.

224 that are homozygous for the disease-related SOD1 mutation.

225 us for a common superoxide dismutase 1 gene (SOD1) mutation.

226 myotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALS(SOD1)) will provide key information

227 However, as SOD1 mutations account for only around 2-5% of ALS cases

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

229 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.

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

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

232 Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS an

233 Herein we report a new SOD1 nanozyme based on PEG-b-poly(aspartate diethyltriam

234 oal catalytically active nanoformulations of SOD1 ("nanozymes") are developed as a modality for treat

235 s) was significantly decreased compared with SOD1(non-A4V) (median survival 6.8 years; p<0.0001, log-

236 capacity decline in SOD1(A4V) compared with SOD1(non-A4V) (p=0.02).

237 atistical significance between SOD1(A4V) and SOD1(non-A4V) (p=0.72, Kruskal-Wallis).

238 n ALS-FRS decline in SOD1(A4V) compared with SOD1(non-A4V) participants (p=0.02) was observed, as wel

239 inguished from other SOD1 mutation patients (SOD1(non-A4V)) for analysis.

240 These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that reg

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

242 ic overexpression of superoxide dismutase 1 (SOD1) or an SOD1 mimetic.

243 ciation of DJ-1 with superoxide dismutase-1 (SOD1), paralleled by significant increases in intracellu

244 Total SOD1 patient median survival was 2.7 years.

245 implementation of clinical trials in the ALS(SOD1) patient population.

246 et was 49.7+/-12.3 years (mean+/-SD) for all SOD1 patients, with no statistical significance between

247 odels have shown decreasing levels of mutant SOD1 protein as a potential therapeutic approach.

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

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

250 tsm) had no effect in liver on either mutant SOD1 protein levels or its activity, indicating a CNS-se

251 associated cytosolic superoxide dismutase 1 (SOD1) protein between motor neurons could be detected in

252 imilarities between the wild-type and mutant SOD1 proteins limit the utility of this approach.

253 We found that expression of ALS mutant SOD1 reduced the level of endogenous Miro1 but did not a

254 Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems.

255 Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic ani

256 d axonal transport of mitochondria in mutant SOD1-related ALS we investigated [Ca2+]c and Miro1 level

257 or its activity, indicating a CNS-selective SOD1 response to the drug.

258 e analyzed the effect of alpha-synuclein and SOD1 seeds in cell culture using protein fragment comple

259 tracerebral injection of alpha-synuclein and SOD1 seeds into SOD1(G93A) transgenic ALS mice.

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

261 1 aggregation in ALS to a nonnative trimeric SOD1 species.

262 These SOD1-specific ALS natural history data will be important

263 LS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in

264 genes have now been linked to ALS, including SOD1, TARDBP (TDP-43), FUS and C9orf72.

265 ns of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2.

266 the proteins that form inclusions of mutant SOD1, TDP-43, and FUS are not merely a subset of the nat

267 These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and

268 l cords of 100-day-old mice carrying a human SOD1 Tg.

269 egenerative disease produced by mutations in SOD1 that cause the enzyme to form toxic oligomers, our

270 itions for high-throughput amyloid assays of SOD1 that enable the control over fibril morphologies an

271 ant version of Cu/Zn superoxide dismutase 1 (SOD1) that is unable to reach native form and that is pr

272 atalytic activity, suppressed the ability of SOD1 to inhibit mitochondrial metabolism at respiratory

273 this NES-like sequence and exports misfolded SOD1 to the cytoplasm.

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

275 ions in the Cu,Zn superoxide dismutase gene (sod1) to amyotrophic lateral sclerosis (ALS) in 1993, re

276 e the specificity of superoxide dismutase-1 (SOD1) to show, for the first time, that H2O2 production

277 SOD1 G93A transgenic mice and in ALS mutant SOD1 transfected cortical neurons, but the underlying me

278 mutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models.

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

280 ncreasing the net negative surface charge of SOD1 via acylation can block the prion-like propagation

281 ng simulations suggested that HTB1M binds to SOD1 via both its alpha-helical and beta-sheet domains a

282 Mean disease duration for all SOD1 was 4.6+/-6.0 and 1.4+/-0.7 years for SOD1(A4V).

283 ysine acylation on the prion-like seeding of SOD1 was assayed in spinal cord extracts of transgenic m

284 ncoding an artificial microRNA against human SOD1 was injected into the cerebral lateral ventricles o

285 Then, using a mouse in which G93A-SOD1 was selectively targeted to the IMS, we demonstrate

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

287 f mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity i

288 For mutated superoxide dismutase 1 (SOD1), which causes familial amyotrophic lateral scleros

289 We focused on Cu-Zn superoxide dismutase (SOD1), which protects cells from oxidative stress.

290 cylase depletion increased K122 acylation on SOD1, which blocked the suppression of respiration in a

291 All assays were performed on D90A apo-SOD1, which is a stable and wild-type-like variant of SO

292 We found that acylation of K122 on SOD1, while not impacting SOD1 catalytic activity, suppr

293 clerosis (ALS) caused by SOD1 mutations (ALS(SOD1)) will provide key information for optimising clini

294 we acylated a fraction of lysine residues in SOD1 with groups of variable hydrophobicity, charge, and

295 ong with the cross-linked polyion complex of SOD1 with polycation poly(ethylene glycol) (PEG)-polylys

296 el of inherited ALS (caused by a mutation in Sod1) with ASOs against Sod1 has been shown to substanti

297 dismutase 1 (SOD1) mouse model of ALS (G93A SOD1) would alter motor function and survival.

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

299 xtracts of transgenic mice expressing a G85R SOD1-yellow fluorescent protein construct.

300 Analogously, SOD1 zinc loss has a detrimental effect on the formation