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| 11173059 | IGF1 | IGF-1 | 1.2 | ciliary neurotrophic factor (CNTF), CNTF and insulin-like growth factor-1 (IGF-1) IGF-1 enhance motor neuron survival in vitro and can also exert | |  |
| 15572176 | IGF1 | IGF-1 | 0.3 | SOD-1 mice expressing increased levels of insulin growth factor-1 (IGF-1) IGF-1 in spinal motor neurons and skeletal muscle 67 | |  |
| 15572176 | IGF1 | IGF-1 | 0.3 | whether these effects are due to an increased release of IGF-1 to the surrounding neuropil targeting glial cells or to a | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | Muscle-specific expression of local Igf-1 (mIgf-1) mIgf-1 isoform also stabilized neuromuscular junctions reduced inflammation in | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | acidic protein Igf insulin-like growth factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | Among these insulin-like growth factor 1 (Igf-1) Igf-1 has been implicated in anabolism of muscle and nerve tissues | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | SOD1 mutant mouse muscle with an adeno-associated virus carrying an Igf-1 gene prolonged life and delayed disease progression ( Kaspar et | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | However it is not clear from that study which Igf-1 isoform was used or whether the effects of Igf-1 expressed | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | which Igf-1 isoform was used or whether the effects of Igf-1 expressed in motor neurons were cell autonomous | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | Two major isoforms of Igf-1 originating from alternative splicing have been described differing in structure | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | as circulating (class class 2 and local (class class 1 Igf-1 | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | Igf-1 class 2 transcripts predominate in the liver are highly growth | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | The contribution to more localized accumulation of Igf-1 class 1 seems due to the combination of exon 1 | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | To assess the effects of supplemental Igf-1 directly on atrophic SOD1 skeletal muscle we exploited a transgenic | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | mouse expressing a full-length precursor of the local isoform of Igf-1 (mIgf-1) mIgf-1 that is normally induced transiently in response to | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | autocrine paracrine manner circumventing the adverse side effects of systemic Igf-1 administration | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | attenuation of motor neuronal degradation and underscore the importance of Igf-1 isoform selection when designing therapeutic strategies for ALS | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | mIgf-1 or indirect action either through distal activation of endogenous Igf-1 expression or through other trophic factors secreted by SOD /mIgf-1 | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | The Igf-1 cDNA used by Kaspar et al | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | The importance of Igf-1 isoform choice in designing therapeutic strategies cannot be overstressed because | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | Organization of the Igf-1 gene | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | As its name implies Igf-1 is similar to insulin in structure | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | The mature Igf-1 is a single-chain protein of 70 aa and differs from | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | The rodent Igf-1 gene contains six exons separated by five introns (Fig Fig | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | to all isoforms as well as part of the mature Igf-1 peptide | |  |
| 15657392 | IGF1 | Igf-1 | 3.5 | region of the E-peptide which is also common to all Igf-1 mRNAs | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | products damage proteins such as insulin-like growth factor 1 (IGF1) IGF1 receptors which are located on motor neurons | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | data indicate that such an oxidative modification hinders the IGF1/Akt IGF1 Akt survival pathway in motor neurons | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Phosphorylation of Akt and cell viability in response to IGF1 recombinant and to H 2 O 2 or activated BV2 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | NADPH Oxidase Impairs the Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | by damaging essential surviving pathways for motor neurons such as IGF1 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | After IGF1 was immunoprecipitated from spinal cord extracts it was probed for | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | This approach failed to reveal evidence of IGF1 oxidation in any of the studied mouse genotypes (data data | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | carbonyl adducts were evident in the _amp_#x003b1 -chain of the IGF1 tyrosine kinase cognate receptor in the spinal cord of symptomatic | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | B similar results were obtained for the _amp_#x003b2 -chain of IGF1 receptor (data data not shown | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | This finding might be quite significant because IGF1 receptors in mouse spinal cords were detected almost exclusively on | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Contrasting with the IGF1 receptor findings oxidation indices in the intracellular serine/threonine serine threonine | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | in the intracellular serine/threonine serine threonine kinase Akt which transduces IGF1 receptor signaling ( 15 did not differ between symptomatic transgenic | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | These results suggest that the entire IGF1 molecular pathway is not oxidatively modified by inflammation in this | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Next we compared selected IGF1 transduction events among the different mouse groups | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Although mutant SOD1 is expressed in all cells markers of IGF1 transduction such as phospho-IGF1 receptor phospho-Akt (data data not shown | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | These data further support the idea that oxidative modification of IGF1 receptor in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Microglial-Derived ROS Recapitulate the IGF1/Akt IGF1 Akt Pathway Defect in Vitro | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | To test the idea that NADPH oxidase-derived ROS could impair IGF1 pathway function an in vitro cell system using the neuron-like | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | were briefly incubated with 0.1_amp_#x02013 100 _amp_#x003bc M human recombinant IGF1 in the presence of overnight-preconditioned serum-free medium supplemented with or | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | to provide a constant flux of H 2 O 2 IGF1 pathway responsiveness was monitored by Akt phosphorylation | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Exposure to IGF1 caused a dose-dependent phosphorylation of Akt in SH-SY5Y cells ( | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Conversely IGF1 barely increased Akt phosphorylation in the neuroblastoma cell lines that | |  |
| 16877542 | IGF1 | IGF1-mediated | 1.5 | of H 2 O 2 ( Fig 5 E attenuated IGF1-mediated Akt phosphorylation in the neuroblastoma cell line ( Fig 5 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | to LPS-activated microglial-conditioned medium the Akt phosphorylation response to the IGF1 recombinant remained depressed and at 72 h a reduction of | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | a reduction of cell viability indistinguishable from the condition without IGF1 was observed ( Fig 5 F | |  |
| 16877542 | IGF1 | IGF1-mediated | 1.5 | However both the alteration of IGF1-mediated Akt phosphorylation and the loss of cell viability mediated by | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Relevant to the latter scenario are our results for IGF1 a trophic factor that is known to promote motor neuron | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | In this study we indeed found that receptors for IGF1 were primarily expressed on motor neurons in mouse spinal cords | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | in mouse spinal cords (Fig Fig 8 and that the IGF1 signaling pathway was impaired by a NADPH oxidase-dependent mechanism in | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Although IGF1 per se did not seem to be damaged by inflammation | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | by inflammation NADPH oxidase did stimulate the oxidative modification of IGF1 receptors ( Fig 4 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | The ligand-dependent kinase activation of IGF1 receptor relies on its arrangement into a heterotetrameric 2_amp_#x003b1;/2_amp_#x003b2;-chain 2_amp_#x003b1 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | It may thus be predicted that oxidation of the IGF1 receptor main extracellular domains (i.e., i.e. the _amp_#x003b1 -chains could | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | molecular events that are normally elicited by ligation of the IGF1 receptor including autophosphorylation and Akt phosphorylation were indeed abated by | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | data also show that microglial NADPH oxidase by impairing the IGF1 signaling pathway renders SH-SY5Y cells in our in vitro system | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Muscle-specific expression of IGF1 stabilizes neuromuscular junctions reduces inflammation in the spinal cord and | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | did not find any evidence that the rescue of the IGF1 pathway by abrogating NADPH oxidase was associated with muscle hypertrophy | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | transgenic SOD1 G93A mice with an adeno-associated virus carrying an IGF1 gene prolongs survival in these animals ( 20 24 | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | but instead may blunt the motor neuron survival response to IGF1 in ALS | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | progression that is seen in patients treated with human recombinant IGF1 ( 25 may be related to the issue raised above | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | It may thus be argued that optimal therapeutic response to IGF1 in diseases such as ALS may rely on a concomitant | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Modulation of the IGF1/Akt IGF1 Akt pathway by NADPH oxidase-derived ROS | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | ( A Immunoprecipitation of IGF1 receptor _amp_#x003b1 -chain followed by OxyBlot (upper upper blot and | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | by OxyBlot (upper upper blot and immunoblot for spinal cord IGF1 receptor _amp_#x003b1 -chain (lower lower blot | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | Glucose oxidase- and microglial-derived ROS impair the IGF1 Akt pathway in vitro | |  |
| 16877542 | IGF1 | IGF1-treated | 1.5 | upper blot and total Akt (lower lower blot immunoblots of IGF1-treated SH-SY5Y cells exposed or not exposed to 75 _amp_#x003bc M | |  |
| 16877542 | IGF1 | IGF1 | 2.0 | ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth factor 1 | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | hypertrophy induced by agents such as insulin-like growth factor-1 (IGF-1) IGF-1 or growth hormone ( Dobrowolny et_amp_#xa0 al. 2005 Kaspar et_amp_#xa0 | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | For the IGF-1 studies not only was there muscle hypertrophy but also concomitant | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | Although in one instance IGF-1 synthesis was mediated by a transgene expressed only by the | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | al. 2005 it has not been established if the secreted IGF-1 acts on the muscle the motor neuron or both | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | al. 2003 and Veldink et_amp_#xa0 al. 2003 with_amp_#xa0 exercise and IGF-1 exhibiting a synergistic effect resulting in an increase in median | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | to nearly uniform disappointment providing little or no benefit for IGF-1 ( Borasio et_amp_#xa0 al. 1998 and Lai et_amp_#xa0 al. 1997 | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | was found to be without benefit but ICV infusion of IGF-1 extended survival in mice ( Nagano et_amp_#xa0 al. 2005a and | |  |
| 17015226 | IGF1 | IGF-1 | 1.2 | precursors including those engineered to produce trophic factors such as IGF-1 are now sensible approaches | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | O 2 _amp_middot _amp_#8722 and decreased insulin-like growth factor-1 (IGF-1) IGF-1 release from microglial cultures and induced motoneuron injury in microglia-motoneuron | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Although IL-4 enhanced release of free IGF-1 from microglia in the absence of lipopolysaccharide it did not | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | in the absence of lipopolysaccharide it did not enhance free IGF-1 release in the presence of lipopolysaccharide | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | of TNF-A and up-regulation of insulin-like growth factor 1 (IGF-1) IGF-1 from microglia ( Butovsky et al 2005 2006 | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | release more nitric oxide and and lower levels of free IGF-1 an active form of the neurotrophic factor | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | This anti-inflammatory cytokine also enhanced free IGF-1 without lipopolysaccharide stimulation | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | However with lipopolysaccharide there was a minimal increase in free IGF-1 yet the cytokine was still neuroprotective | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis MN | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | MN USA was used to determine the concentration of free IGF-1 protein in cell culture supernatant | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | h 100 _amp_#x03BC L of either sample or standard rat IGF-1 (Diagnostic Diagnostic Systems Laboratories Webster TX USA was added to | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Lipopolysaccharide-activated microglia increased production of nitric oxide and decreased free IGF-1 In our previous study we demonstrated that nitric oxide plays | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | In the present experiments levels of free IGF-1 as well as nitric oxide were measured in microglia activated | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | We also assayed the levels of free IGF-1 in microglia cultures given that only free IGF-1 is active | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | of free IGF-1 in microglia cultures given that only free IGF-1 is active | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | the presence of 1 _amp_#x03BC;g/mL _amp_#x03BC g mL lipopolysaccharide free IGF-1 concentrations were significantly lower than untreated microglia ( Fig 1b | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | In MN Mc cocultures lipopolysaccharide decreased free IGF-1 in a dose-dependent manner ( Fig 2b | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | m MN lipopolysaccharide 1.02 _amp_plusmn 0.10 _amp_#x03BC m and free IGF-1 levels (MN MN only 1.95 _amp_plusmn 0.31 pg/mL, pg mL | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | were all close to background indicating that nitrite nitrate and IGF-1 were produced by microglia | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Free IGF-1 did not increase after addition of IL-4 to lipopolysaccharide-activated microglia | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | to lipopolysaccharide-activated microglia In Fig 1b we noted less free IGF-1 in the culture media following microglial activation with lipopolysaccharide | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | To determine whether IGF-1 production was influenced by IL-4 the levels of free IGF-1 | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | IGF-1 production was influenced by IL-4 the levels of free IGF-1 were measured in microglia monocultures or MN Mc cocultures | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | In cultures without lipopolysaccharide IL-4 significantly increased levels of free IGF-1 ( Fig 9a b | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | The free IGF-1 of motoneuron only cultures were close to background level in | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | indicating that microglia were the source of the increased free IGF-1 after IL-4 treatment | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | However the levels of free IGF-1 did not change significantly in lipopolysaccharide-activated microglia or in MN | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Similar results were seen when IGF-1 mRNA levels were measured with and without IL-4 (data data | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | finding in the current study is that IL-4 increased free IGF-1 the active form of this neuroprotective factor in untreated microglia | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | factor in untreated microglia cultures and that lipopolysaccharide decreased free IGF-1 | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | At first we hypothesized that the induction of free IGF-1 in microglia might be another aspect of IL-4 neuroprotection however | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | lipopolysaccharide-treated MN Mc cocultures however IL-4 did not increase free IGF-1 levels in the same cocultures | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | In addition we saw no increase in IGF-1 mRNA in these lipopolysaccharide-activated cultures although it has been reported | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | lipopolysaccharide-activated cultures although it has been reported that IL-4 up-regulated IGF-1 mRNA in both untreated and lipopolysaccharide-activated microglia ( Butovsky et | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Additionally even though free IGF-1 was up-regulated by IL-4 in untreated microglia cocultured with motoneurons | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Finally we also found a poor correlation between free IGF-1 levels and motoneuron survival in MN Mc cocultures | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Therefore these results suggest that IGF-1 may not be the primary mechanism of IL-4 neuroprotection | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Firstly IGF-1 is clearly a generally neuroprotective trophic factor that has been | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | that there may have been an immediate local increase in IGF-1 that was quickly sequestered by binding proteins it is likely | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | sequestered by binding proteins it is likely that the free IGF-1 levels induced by IL-4 either before or after lipopolysaccharide in | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of the five known binding proteins ( | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | et al 2005 there may have been increases in both IGF-1 and one or more of the binding proteins that resulted | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | binding proteins that resulted in no net change in free IGF-1 | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | Finally it is possible that neurotrophic factors other than IGF-1 may enhance the neuroprotective actions of this anti-inflammatory cytokine | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | free radicals released from microglia and may not involve free IGF-1 | |  |
| 17018025 | IGF1 | IGF-1 | 3.5 | IL-10 increased microglial release and also decreased rather than increased IGF-1 release from microglia (data data not shown | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | nitric oxide more superoxide and less insulin-like growth factor-1 (IGF-1) IGF-1 than wild-type microglia | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | The supernatants were collected for nitric oxide and IGF-1 assays and the cells were collected for western analyses | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | supernatants of the co-cultures were collected for nitric oxide and IGF-1 assays and the cells on the coverslips were fixed with | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | ELISA for IGF-1 Insulin-like growth factor-1 ELISA Duoset kit (R R _amp_ D | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Minneapolis MN USA was used to determine the concentrations of IGF-1 in cell culture supernatants | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | the addition of 100 _amp_#x03BC L of samples or mouse IGF-1 standard and incubated for 2 h at 22_amp_deg C | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type microglia | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | other previous studies demonstrated that microglia produce significant amounts of IGF-1 ( Butovsky et al 2005 Zhao et al 2006 we | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | 2005 Zhao et al 2006 we measured the presence of IGF-1 in the supernatants of the untreated and LPS-treated microglia cultures | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | There was 1100 _amp_plusmn 180 pg/mL pg mL IGF-1 in the untreated wild-type microglia supernatants which was set at | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type microglia ( p _lt_ 0.01 ( | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | with 10 or 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A microglia | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia (10 10 ng/mL ng mL LPS 21 | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | 2.4% from wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.01 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 18 | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | 2.2% in wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.05 | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | treatment mSOD1 G93A microglia released significantly more superoxide and less IGF-1 than wild-type microglia suggesting that mSOD1 G93A microglia are more | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | presence of 100 times less LPS although the amount of IGF-1 released was small mSOD1 G93A microglia did not release significantly | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | was small mSOD1 G93A microglia did not release significantly more IGF-1 than wild-type microglia treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | microglia co-cultured with motoneurons produce more nitric oxide and less IGF-1 than wild-type microglia Because we demonstrated that primary cultures of | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS both co-cultures released less IGF-1 (37 37 _amp_plusmn 2.1% in wild-type microglia and 26 _amp_plusmn | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | However mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures released significantly less IGF-1 (30% 30% decrease than wild-type microglia/motoneuron microglia motoneuron co-cultures ( | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | microglia co-cultured with motoneurons produced more nitric oxide and less IGF-1 than wild-type microglia we asked whether mSOD1 G93A microglia would | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | not observe significant increase of nitric oxide superoxide or less IGF-1 from wt-hSOD1 microglia compared with their littermate controls ( Table | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Among these neurotrophic factors IGF-1 has been shown to have a protective effect on motoneurons | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | IGF-1 is a potent neurotrophic and survival factor ( Vincent et | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | In contrast free IGF-1 levels in ALS patients_amp_#8217 spinal cords and serum were shown | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | al 1998 Wilczak et al 2003 suggesting that down-regulation of IGF-1 trophic support may lead to degeneration of motoneurons | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | IGF-1 has been reported to prevent glutamate-induced embryonic rat spinal cord | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | and delayed disease progression in transgenic ALS mice by enhancing IGF-1 expression in motoneurons | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | A recent study showed that intrathecal injection of IGF-1 into the lumbar spinal cord of transgenic mice expressing the | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Following activation with LPS the current study demonstrated that free IGF-1 levels were significantly reduced to 20-30% of untreated controls | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | represent the first demonstration that wild-type microglia released more free IGF-1 than microglia from mSOD1 G93A transgenic mice either with or | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Therefore more IGF-1 neurotrophic support from wild-type microglia may also contribute to the | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | Additionally wild-type microglia may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | G93A microglia released more nitric oxide more superoxide and less IGF-1 | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | wt-hSOD1 microglia produce similar amounts of nitric oxide superoxide and IGF-1 compared with their wild-type littermates | |  |
| 17555556 | IGF1 | IGF-1 | 1.2 | mice by producing more nitrite oxide and superoxide and less IGF-1 | |  |
| 11173059 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | neurotrophic factors such as brain derived neurotrophic factor bdnf ciliary neurotrophic factor cntf and insulin like growth factor 1 igf 1 enhance motor neuron survival in vitro and can also exert beneficial effects in mouse models of amyotrophic lateral sclerosis reviewed in yuen and mobley 1996 . | |  |
| 11173059 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | brain derived neurotrophic factor levels are decreased in alzheimer disease hippocampi ferrer et al. 1999 and insulin like growth factor 1 shows protective effects against _amp_#x3b2; amyloid protein neurotoxicity dore et al. 1999 . | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | recombinant human insulin like growth factor i rhigf i for amyotrophic lateral sclerosis/motor neuron disease. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | background: trophic factors including recombinant human insulin like growth factor i have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | randomised clinical trials of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis to date have yielded conflicting results. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | objectives: the main objective of this review was to examine the efficacy of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | search strategy: a search was carried out using the cochrane neuromuscular disease group register for randomised clinical trials of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | enquiries were also made of authors of randomised clinical trials as well as the manufacturers of recombinant human insulin like growth factor i regarding any other randomised clinical trials which had not yet been published. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | selection criteria: types of studies: all randomised controlled clinical trials involving recombinant human insulin like growth factor i treatment of amyotrophic lateral sclerosis. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | types of interventions: treatment with recombinant human insulin like growth factor i or placebo. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | types of outcome measures: primary: change in appel amyotrophic lateral sclerosis rating scale aalsrs total score with 0.1mg/kg/day of recombinant human insulin like growth factor i after nine months treatment. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | secondary: change in aalsrs with recombinant human insulin like growth factor i 0.1mg/kg/day and 0.05mg/kg/day at 1 2 3 4 5 6 7 8 9 months change in quality of life sickness impact profile scale survival and adverse events. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | main results: the primary outcome measure was change in disease progression as determined by the appel als rating scale total score with 0.1 mg/kg/day of recombinant human insulin like growth factor i subcutaneously after nine months treatment. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | the level of significance was lower in the european trial which compared 59 patients on placebo with 124 on insulin like growth factor i 0.1 mg/kg/day weighted mean difference 3.30 95%ci 8.68 to 2.08 than in the north american trial which compared 90 patients on placebo with 89 on recombinant human insulin like growth factor i 0.05 | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | i 0.1 mg/kg/day weighted mean difference 3.30 95%ci 8.68 to 2.08 than in the north american trial which compared 90 patients on placebo with 89 on recombinant human insulin like growth factor i 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day weighted mean difference 6.00 95%ci 10.99 to 1.01 . | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | the secondary outcome measures showed similar trends favouring recombinant human insulin like growth factor i but these did not reach significance at the five per cent level. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | similarly the data with the 0.05mg/kg/day dose showed trends favouring recombinant human insulin like growth factor i at all time points but did not reach significance at the five per cent level at any point. | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | evaluation of adverse events showed an increased risk of injection site reactions/inflammation with recombinant human insulin like growth factor i relative risk 2.53 95% ci 1.40 to 4.59 . | |  |
| 12137643 | insulin like growth factor | insulin like growth factor | 1.0 | reviewer's conclusions: recombinant human insulin like growth factor i may be modestly effective but the evidence currently available is insufficient for a definitive assessment. | |  |
| 15657392 | insulin like growth factor | insulin like growth factor | 1.0 | here we show that muscle restricted expression of a localized insulin like growth factor igf 1 isoform maintained muscle integrity and enhanced satellite cell activity in sod1 transgenic mice inducing calcineurin mediated regenerative pathways. | |  |
| 15657392 | insulin like growth factor | insulin like growth factor | 1.0 | abbreviations used in this paper: achr acetylcholine receptor; als amyotrophic lateral sclerosis; cna calcineurin; gfap glial fibrillary acidic protein; igf insulin like growth factor; migf 1 local isoform of igf 1; myhc myosin heavy chain; sod1 superoxide dismutase1; wt wild type. | |  |
| 15657392 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | among these insulin like growth factor 1 igf 1 has been implicated in anabolism of muscle and nerve tissues inducing muscle hypertrophy and promoting neuronal survival musar_amp_ograve; and rosenthal 2002 . | |  |
| 16877542 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | we also show that nadph oxidase derived oxidant products damage proteins such as insulin like growth factor 1 igf1 receptors which are located on motor neurons. | |  |
| 16877542 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | nadph oxidase impairs the insulin like growth factor 1 igf1 /akt pathway in transgenic sod1 g93a mice. | |  |
| 16877542 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | ros reactive oxygen species sod1 superoxide dismutase 1 igf1 insulin like growth factor 1 | |  |
| 17015226 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | on the other hand muscle hypertrophy induced by agents such as insulin like growth factor 1 igf 1 or growth hormone dobrowolny et_amp_#xa0;al. 2005 kaspar et_amp_#xa0;al. 2003 and kaspar et_amp_#xa0;al. 2005 has led to significant life extensions in als transgenic mice. | |  |
| 17018025 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | tivated by lipopolysaccharide as well as to activated microglia cocultured with primary motoneurons. lipopolysaccharide increased nitric oxide and superoxide o 2 _amp_middot;_amp_#8722; and decreased insulin like growth factor 1 igf 1 release from microglial cultures and induced motoneuron injury in microglia motoneuron cocultures. | |  |
| 17018025 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | recently it has been documented that protection of il 4 was attributed to down regulation of tnf a and up regulation of insulin like growth factor 1 igf 1 from microglia butovsky et al 2005 2006 . | |  |
| 17555556 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | following activation with lipopolysaccharide msod1 g93a microglia released more nitric oxide more superoxide and less insulin like growth factor 1 than wild type microglia. | |  |
| 17555556 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | our results demonstrate that msod1 g93a mouse microglia release more nitric oxide more superoxide and less insulin like growth factor 1 igf 1 than wild type microglia. | |  |
| 17555556 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | elisa for igf 1 insulin like growth factor 1 elisa duoset kit r _amp_ d systems minneapolis mn usa was used to determine the concentrations of igf 1 in cell culture supernatants. | |  |
| 17555556 | insulin-like growth factor 1 | insulin like growth factor 1 | 1.0 | insulin like growth factor 1 is a potent motoneuron trophic and survival factor. | |  |