)| PMID |
12843244 ( ) |
|---|---|
| Title | Dissociation between neurodegeneration and caspase-11-mediated activation of caspase-1 and caspase-3 in a mouse model of amyotrophic lateral sclerosis. |
| Abstract | Caspase-11 is a key regulator of caspase-1 and caspase-3 activation under pathological conditions. We show here that the expression of caspase-11 is upregulated in the spinal cord of superoxide dismutase 1 (SOD1) G93A transgenic mice, a mouse model of amyotrophic lateral sclerosis (ALS), before the onset of motor dysfunction and remains at the high levels throughout the course of disease. The caspase-1- and caspase-3-like activities, as well as the level of interleukin-1beta, were significantly reduced in the spinal cord of symptomatic caspase-11-/-;SOD1 G93A mice compared with that of caspase-11+/-; SOD1 G93A mice. However, neurodegeneration, inflammatory responses, and the disease onset and progression in SOD1 G93A transgenic mice were not altered by the ablation of caspase-11 gene. Thus, although caspases may contribute to certain aspects of pathology in this mouse model of ALS, their inhibition is not sufficient to prevent neurodegeneration. Our study urges caution when considering the inhibition of caspases as a direct therapeutic method for the treatment of chronic neurodegenerative diseases. 02115, USA. Neuroscience |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 28 | superoxide dismutase 1 | SOD-expressing | SOD1 | SOD1-mediated | |
| 5992 | IL1B | interleukin 1, beta | 27 | IL-1 | il 1 | interleukin 1 beta | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 26 | caspase 1 | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 15 | caspase 3 | |
| 4235 | GFAP | glial fibrillary acidic protein | 3 | GFAP-positive | glial fibrillary acidic protein | |
| 1509 | CASP8 | caspase 8, apoptosis-related cysteine peptidase | 2 | caspase 8 | caspase-8 | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 2 | Bcl-2 | bcl 2 | |
| 1508 | CASP7 | caspase 7, apoptosis-related cysteine peptidase | 1 | caspase 7 | |
| 5991 | IL1A | interleukin 1, alpha | 1 | interleukin 1 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 1 | Fas | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | upregulated in the spinal cord of superoxide dismutase 1 (SOD1) SOD1 G93A transgenic mice a mouse model of amyotrophic lateral sclerosis |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | in the spinal cord of symptomatic caspase-11 -/-;SOD1 - - SOD1 G93A mice compared with that of caspase-11 +/-; - SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | SOD1 G93A mice compared with that of caspase-11 +/-; - SOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | neurodegeneration inflammatory responses and the disease onset and progression in SOD1 G93A transgenic mice were not altered by the ablation of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | Key words ALS motor neuron degeneration neurodegeneration SOD1 caspase apoptosis |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | several mutations in the Cu /Zn Zn superoxide dismutase (SOD1) SOD1 are causally responsible for a subset of familial ALS (FALS) |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | Consistent with a causal role of SOD1 mutations in FALS transgenic mice expressing human SOD1 mutants develop |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | role of SOD1 mutations in FALS transgenic mice expressing human SOD1 mutants develop age-dependent progressive motor neuron degeneration with cellular pathological |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | of caspase-1 and caspase-3 in the spinal cords of mutant SOD1 mice and ALS patients has been reported previously (Martin, Martin |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | the onset and progression of the disease symptoms in G93A SOD1 (G93A) G93A transgenic mice (Friedlander Friedlander et al. 1997 Li |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | under pathological conditions (Wang Wang et al. 1998 beta (IL-1 IL-1 beta maturation and resistant to lipopolysaccharide (LPS)-induced LPS -induced septic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 3.2 | of ALS a critical role of individual caspases in mutant SOD1-mediated neurodegeneration has not been examined in different caspase mutant mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | in relation to the early events of pathogenesis in mutant SOD1 transgenic mice such as mitochondrial dilation neurofilament abnormality and glutamate |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | Mouse lines expressing human SOD1 mutant G93A [C57BL/6J-TgN(SOD1-G93A)1Gurdl] C57BL 6J-TgN SOD1-G93A 1Gurdl were obtained from |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | To minimize the variations in genetic background one SOD1 G93A transgenic male mouse was mated with one female caspase-11 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | An F1 male mouse (caspase-11+/-;SOD1 caspase-11 - SOD1 G93A was mated with two caspase-11 - -mice and one |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | Antibodies against human- and mouse-specific SOD1 were obtained from Chemicon (Temecula, Temecula CA |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | Furthermore because caspase-11 plays a key role in regulating IL-1 beta maturation in LPS-stimulated mice (Wang Wang et al. 1998 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | demonstrating that the neural degeneration and accelerated death of G37R SOD1 mice are not altered in the background of IL-1 beta- |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | G37R SOD1 mice are not altered in the background of IL-1 beta- -mice (Nguyen Nguyen et al. 2001 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | These results suggest that the expression of G93A SOD1 may induce neurodegeneration through multiple pathways that may involve multiple |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | in the absence of caspase-11 Because the complete elimination of IL-1 beta in IL-1 beta- -mice did not alter the disease |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | of caspase-11 Because the complete elimination of IL-1 beta in IL-1 beta- -mice did not alter the disease course of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | IL-1 beta- -mice did not alter the disease course of SOD1 G37R mice (Nguyen Nguyen et al. 2001 the most likely |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | Motor neurons expressing mutant SOD1 have been shown to have an enhanced sensitivity toward Fas-induced |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.3 | (Raoul Raoul et al. 2002 although the critical role of Fas pathway in mediating motor neuron degeneration has not been evaluated |
| 1509 | CASP8 | caspase 8, apoptosis-related cysteine peptidase | caspase-8 | 2.0 | this regard it is worth noting that the activation of caspase-8 and -9 was found only at the end stage of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD-expressing | 3.2 | -9 was found only at the end stage of mutant SOD-expressing transgenic mice (Gu_amp_eacute;gan Gu_amp_eacute gan et al. 2001 2002 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | However the weak protection by Bcl-2 overexpression in a mouse model of ALS (Kostic Kostic et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | The exact parallels between SOD1 mutant transgenic mice and human ALS are not clear because |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | C Reduction of IL-1 beta level in the absence of caspase-11 in the caspase-11-/-; |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | at indicated days of age and the level of mature IL-1 beta was measured by ELISA ( n = 4 mean_amp_#177 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | D The expression of the human mutant SOD1 protein is not affected by the absence of caspase-11 in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | mouse-specific anti-SOD1 antibodies for the detection of introduced and endogenous SOD1 proteins respectively |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | The secretion and maturation of IL-1 beta is another downstream indicator of caspase-11-caspase-1 pathway (Kuida Kuida |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | The increase in IL-1 beta levels was first detected at approximately day 90 and |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | The levels of IL-1 beta in the spinal cords of caspase-11 -/-; - - |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | indicates that caspase-11 also plays a key role in regulating IL-1 beta levels in the G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | caspase-11 gene affected the expression level of the human mutant SOD1 protein in the double-mutant mice we compared the levels of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | of caspase-11 did not alter the expression of the mutant SOD1 protein in the double-mutant mice |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | the activities of its downstream caspases-1 and -3 and also IL-1 beta levels during the pathogenesis of this model of FALS |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | compared the numbers of microglia and astrocytes using MacI and GFAP as their respective markers in the spinal cords of caspase-11 |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP-positive | 2.5 | showed dramatic increases in the number of MacI-positive microglia and GFAP-positive astrocytes with no significant differences in the absence or presence |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | suggests that despite the significant reduction of caspase activation and IL-1 beta levels in caspase-11 -/-; - - G93A mice the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 5.5 | - - G93A mice the inflammatory response induced by mutant SOD1 was not significantly altered |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | caspase 11 is a key regulator of caspase 1 and caspase 3 activation under pathological conditions. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | caspase 11 is a key regulator of caspase 1 and caspase 3 activation under pathological conditions. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | we show here that the expression of caspase 11 is upregulated in the spinal cord of superoxide dismutase 1 sod1 g93a transgenic mice a mouse model of amyotrophic lateral sclerosis als before the onset of motor dysfunction and remains at the high levels throughout the course of disease. |
| 5992 | IL1B | interleukin 1, beta | interleukin 1 beta | 1.0 | the caspase 1 and caspase 3 like activities as well as the level of interleukin 1 beta were significantly reduced in the spinal cord of symptomatic caspase 11 / ;sod1 g93a mice compared with that of caspase 11 +/ ; sod1 g93a mice. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the caspase 1 and caspase 3 like activities as well as the level of interleukin 1 beta were significantly reduced in the spinal cord of symptomatic caspase 11 / ;sod1 g93a mice compared with that of caspase 11 +/ |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | the caspase 1 and caspase 3 like activities as well as the level of interleukin 1 beta were significantly reduced in the spinal cord of symptomatic caspase 11 / ;sod1 g93a mice compared with that of caspase 11 +/ ; sod1 g93a mi |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | activation of caspase 1 and caspase 3 in the spinal cords of mutant sod1 mice and als patients has been reported previously martin 1999 ; li et al. 2000 ; pasinelli et al. 2000 ; vukosavic et al. 2000 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | activation of caspase 1 and caspase 3 in the spinal cords of mutant sod1 mice and als patients has been reported previously martin 1999 ; li et al. 2000 ; pasinelli et al. 2000 ; vukosavic et al. 2000 . |
| 1508 | CASP7 | caspase 7, apoptosis-related cysteine peptidase | caspase 7 | 1.0 | more recently activation of caspase 7 8 and 9 in a mouse model at end stage of the disease has been also reported gu_amp_eacute;gan et al. 2001 2002 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | moreover inhibition of caspase s with peptide inhibitors or by introducing a dominant negative mutant of caspase 1 delayed the onset and progression of the disease symptoms in g93a sod1 g93a transgenic mice friedlander et al. 1997 ; li et al. 2000 suggesting the importance of caspase mediated apoptosis in the als |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | esis of als strongly suggested the involvement of caspase 11 in this process because caspase 11 is a key upstream regulator of both caspase 1 and 3 under pathological conditions wang et al. 1998 beta il 1 beta maturation and resistant to lipopolysaccharide lps induced septic shock wang et al. 1998 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the possible involvement of both caspase 1 and caspase 3 in the pathogenesis of als strongly suggested the involvement of caspase 11 in this process because caspase 11 is a key upstream regulator of both caspase 1 and 3 under pathological con |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | and caspase 3 in the pathogenesis of als strongly suggested the involvement of caspase 11 in this process because caspase 11 is a key upstream regulator of both caspase 1 and 3 under pathological conditions wang et al. 1998 beta il 1 beta maturation and resistant to lipopolysaccharide lps induced septic shock wang et al. 1998 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | the possible involvement of both caspase 1 and caspase 3 in the pathogenesis of als strongly suggested the involvement of caspase 11 in this process because caspase 11 is a key upstream regulator of both caspase 1 and 3 under pathological conditions wang e |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | apoptosis and caspase 3 activation by lps shock or ischemic brain injury are also defective in caspase 11 / mice kang et al. 2000 2002 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | in the present study we provide evidence that caspase 11 plays a critical role in caspase 1 and 3 activation during pathogenesis of g93a mice a mouse model of fals gurney et al. 1994 . |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | immunostaining of anti maci macrophage antigen i caltag burlingame ca anti gfap glial fibrillary acidic protein or anti neun neuronal specific nuclear protein chemicon temecula ca antibody and terminal deoxynucleotidyl transferase mediated biotinylated utp nick end labeling tunel assay were done using methods |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | caspase 11 regulates caspase 1 and 3 activation in the spinal cords of g93a mice |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | activation of caspase 1 and caspase 3 in the spinal cord of presymptomatic g93a mice has been reported previously li et al. 2000 ~60 d of age consistent with reports of active caspase 1 being present in the spinal cords of g93a mice li et al. 2000 ; pasinelli et al. 2000 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | activation of caspase 1 and caspase 3 in the spinal cord of presymptomatic g93a mice has been reported previously li et al. 2000 ~60 d of age consistent with reports of active caspase 1 being present in the spinal cords of g93a mice li e |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | furthermore our analysis demonstrated a clear induction of full length caspase 1 expression starting from 60 d of age and continuing to increase as the disease progresses fig 1 a . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | low levels of active caspase 3 were first detected at day 60 in g93a mice at approximately the time of caspase 11 induction. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | however no signs of caspase 1 and 3 activation were detected in the caspase 11 / ; g93a spinal cords data not shown . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | these results imply that caspase 11 in addition to caspase 1 and 3 may be involved in regulating inflammatory reaction and/or apoptosis during the disease onset and progression of this mouse model of als. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | because the lack of caspase 11 resulted in the significant inhibition of caspase 1 and caspase 3 activation our results suggest that caspase 1 and caspase 3 activation is not crucial for neurodegeneration in this mouse model of als. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | because the lack of caspase 11 resulted in the significant inhibition of caspase 1 and caspase 3 activation our results suggest that caspase 1 and caspase 3 activation is not crucial for neurodegeneration in this mouse model of als. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | furthermore because caspase 11 plays a key role in regulating il 1 beta maturation in lps stimulated mice wang et al. 1998 beta is not a key determinant in mediating neurodegeneration or the inflammatory response in this model. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | this is consistent with the report demonstrating that the neural degeneration and accelerated death of g37r sod1 mice are not altered in the background of il 1 beta / mice nguyen et al. 2001 . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the spinal cord of g93a mice was not affected by the caspase 11 deficiency indicating that the overall inflammatory response proceeded in the absence of caspase 11 because the complete elimination of il 1 beta in il 1 beta / mice did not alter the disease course of sod1 g37r mice nguyen et al. 2001 the most likely interpretation is that g93a induces inflammatory responses through multiple or redundant |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | beta in il 1 beta / mice did not alter the disease course of sod1 g37r mice nguyen et al. 2001 the most likely interpretation is that g93a induces inflammatory responses through multiple or redundant pathways. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | our study cannot rule out however that the residual caspase activity in caspase 11 / background sufficient for neurodegeneration and caspases other than caspase 1 and caspase 3 may be involved in mediating neuronal degeneration in g93a mice. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | our study cannot rule out however that the residual caspase activity in caspase 11 / background sufficient for neurodegeneration and caspases other than caspase 1 and caspase 3 may be involved in mediating neuronal degeneration in g93a mice. |
| 1509 | CASP8 | caspase 8, apoptosis-related cysteine peptidase | caspase 8 | 1.0 | in this regard it is worth noting that the activation of caspase 8 and 9 was found only at the end stage of mutant sod expressing transgenic mice gu_amp_eacute;gan et al. 2001 2002 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | however the weak protection by bcl 2 overexpression in a mouse model of als kostic et al. 1997 suggests an involvement of alternative cell death mechanisms as well. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | we showed previously that introduction of dominant negative caspase 1 c281g mutant in g93a mice delayed the disease onset and progression friedlander et al. 1997 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | because caspase 1 interacts with caspase 11 wang et al. 1998 this dominant negative mutant of caspase 1 may act by inhibiting caspase 11. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | however because the deletion of caspase 11 did not prevent neurodegeneration in the g93a mice it is possible that caspase 1c281g may act by inhibiting caspases other than caspase 1 11 or 3 or by another unknown gain of function process. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | upregulation of caspase 11 at the disease onset in g93a mice and reduction of caspase 1 and caspase 3 activation in caspase 11 / ;g93a double mutant mice. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | upregulation of caspase 11 at the disease onset in g93a mice and reduction of caspase 1 and caspase 3 activation in caspase 11 / ;g93a double mutant mice. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | a upregulation of caspase 11 and appearance of active caspase 1 and caspase 3 fragments in the g93a spinal cords. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | a upregulation of caspase 11 and appearance of active caspase 1 and caspase 3 fragments in the g93a spinal cords. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | eighty micrograms of the samples were also immunoblotted with monoclonal anti caspase 1 antibody for detection of full length caspase 1 c1fl and the active form active c1 and with anti active caspase 3 antibody active c3 . *igg h igg heavy chain; *nsp nonspecific. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | eighty micrograms of the samples were also immunoblotted with monoclonal anti caspase 1 antibody for detection of full length caspase 1 c1fl and the active form active c1 and with anti active caspase 3 antibody active c3 . *igg h igg heavy chain; *nsp nonspecific. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the caspase 3 caspase 1 and caspase 11 like enzyme activities were measured using fluorogenic substrates acdevd amc devd acyvad amc yvad and acvehd amc vehd respectively in the lysates n = 4; mean _amp_#177; sd . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | the caspase 3 caspase 1 and caspase 11 like enzyme activities were measured using fluorogenic substrates acdevd amc devd acyvad amc yvad and acvehd amc vehd respectively in the lysates n = 4; mean _amp_#177; sd . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | c reduction of il 1 beta level in the absence of caspase 11 in the caspase 11 / ; g93a spinal cords. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | spinal cords from caspase 11; g93a mice were taken at indicated days of age and the level of mature il 1 beta was measured by elisa n = 4; mean_amp_#177;sd . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | to examine whether caspase 11 indeed regulates caspase 1 and/or 3 in the spinal cord of g93a mice we crossed caspase 11 / and g93a mice and compared the profiles of caspase activities in the symptomatic day 120 spinal cord lysates of littermate caspase 11 |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | consistent with the activation of caspase 1 and caspase 3 and the caspase 11 induction profile by immunoblot fig 1 a acyvad amc caspase 1 like acdevd amc caspase 3 like and acvehd amc caspase 11 like cleavage activities thornberry et al. 1997 ; kang et al. 2000 were elevated in the lumbar and thoracic spinal cords of g93a mice fig 1 b |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | consistent with the activation of caspase 1 and caspase 3 and the caspase 11 induction profile by immunoblot fig 1 a acyvad amc caspase 1 like acdevd amc caspase 3 like and acvehd amc caspase 11 like cleavage activities thornberry et al. 1997 ; kang et al. 2000 were elevated in the lumbar and thoracic spinal cords of g93a mice fig 1 b . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | in caspase 11 / ; g93a mice the absence of caspase 11 resulted in a significant reduction of caspase 3 and caspase 1 like activities as well as caspase 11 like activity fig 1 b . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in caspase 11 / ; g93a mice the absence of caspase 11 resulted in a significant reduction of caspase 3 and caspase 1 like activities as well as caspase 11 like activity fig 1 b . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the secretion and maturation of il 1 beta is another downstream indicator of caspase 11 caspase 1 pathway kuida et al. 1995 beta in wild type control caspase 11 +/ ; g93a and caspase 11 / ; g93a mice by elisa fig 1 c . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the secretion and maturation of il 1 beta is another downstream indicator of caspase 11 caspase 1 pathway kuida et al. 1995 beta in wild type control caspase 11 +/ ; g93a and caspase 11 / ; g93a mice by elisa fig 1 c . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the increase in il 1 beta levels was first detected at approximately day 90 and remained at higher levels at later time points. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the levels of il 1 beta in the spinal cords of caspase 11 / ; g93a mice were consistently lower than that of caspase 11 +/ ; g93a mice. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | this result indicates that caspase 11 also plays a key role in regulating il 1 beta levels in the g93a mice. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | together these results suggest that caspase 11 is activated and regulates the activities of its downstream caspases 1 and 3 and also il 1 beta levels during the pathogenesis of this model of fals. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the evidence of activation of caspase 1 and 3 by caspase 11 in g93a mice prompted us to compare the inflammatory response and cell death in g93a spinal cords in the presence or absence of caspase 11. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | this result suggests that despite the significant reduction of caspase activation and il 1 beta levels in caspase 11 / ; g93a mice the inflammatory response induced by mutant sod1 was not significantly altered. |
| 5991 | IL1A | interleukin 1, alpha | interleukin 1 | 1.0 | interleukin 1|sod1 g93a protein|superoxide dismutase|casp3 protein human|casp11 protein mouse|casp3 protein mouse|caspase 3|caspases|caspase 1| |