)| PMID |
18436268 ( ) |
|---|---|
| Title | Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice. |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by selective degeneration of motor neurons. Mutations in copper/zinc superoxide dismutase (SOD1) account for 20% cases of familial ALS (fALS), but the underlying pathogenetic mechanisms are largely unknown. Using SOD1(G93A) mice model of ALS, we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine (Hcy). To investigate whether Hcy-lowering therapy is beneficial to this disease, we applied folic acid (FA) and vitamin B12 which are important factors involved in the Hcy metabolism to assess the neuroprotective effect of FA and B12 in the SOD1(G93A) mice. Our results showed FA or FA+B12 treatment significantly delayed the disease onset and prolonged the lifespan, accompanied by the significant reduction of motor neuron loss. Furthermore, we found that FA or FA+B12 treatment significantly attenuated the plasma Hcy level, suppressed the activation of microglia and astrocytes, and inhibited the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord. Moreover, FA or FA+B12 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose)polymerase (PARP) but up-regulated the level of anti-apoptotic protein Bcl-2. However, B12 treatment alone did not show any significant benefit to this disease. These results provide evidence to demonstrate that elevated Hcy is involved in the pathogenesis of fALS and FA therapy may have therapeutic potential for the treatment of the disease. Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, PR China. |
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)) | 67 | SOD1 | superoxide dismutase | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 29 | Bcl-2 | bcl 2 | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 16 | iNOS | nitric oxide synthase | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 15 | tumor necrosis factor alpha | TNF-A | |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | 12 | PARP | poly adp ribose polymerase | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 11 | caspase 3 | |
| 4235 | GFAP | glial fibrillary acidic protein | 4 | glial fibrillary acidic protein | GFAP | |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | 3 | CD11b | |
| 5215 | HSD17B7 | hydroxysteroid (17-beta) dehydrogenase 7 | 2 | PRAP | |
| 132 | ACTB | actin, beta | 2 | beta actin | beta-actin | |
| 2367 | CRP | C-reactive protein, pentraxin-related | 1 | c reactive protein | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 1 | interleukin 6 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Mutations in copper/zinc copper zinc superoxide dismutase (SOD1) SOD1 account for 20% cases of familial ALS (fALS), fALS but |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Using SOD1 G93A mice model of ALS we demonstrated that mutation in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | G93A mice model of ALS we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | assess the neuroprotective effect of FA and B12 in the SOD1 G93A mice |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | and inhibited the expression of inducible nitric oxide synthase (iNOS) iNOS and tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 in spinal cord |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | nitric oxide synthase (iNOS) iNOS and tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 in spinal cord |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | levels of cleaved caspase-3 and poly(ADP-ribose)polymerase poly ADP-ribose polymerase (PARP) PARP but up-regulated the level of anti-apoptotic protein Bcl-2 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | polymerase (PARP) PARP but up-regulated the level of anti-apoptotic protein Bcl-2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | the gene encoding for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 ( Al-Chalabi and Leigh 2000 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Over-expression of mutant SOD1 gene in mice causes a progressive motor neuron disease resembling |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | In this study we used SOD1 G93A mice model to study the association of homocysteine (Hcy) |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | that Hcy-immunoreactive astrocytes presented in the spinal cord of symptomatic SOD1 G93A mice and Hcy even at the physiological concentration induced |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | concentration induced significant cytotoxicity in neuronal cell-line transfected with mutant SOD1 gene suggesting Hcy may play an important role in the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | of Hcy increased the expression of inflammatory factors such as TNF-_amp_#x3b1 and promoted reactive oxygen species (ROS) ROS as well as |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | can lower the Hcy level and provide the neuroprotection in SOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The colony of well-characterized TgN (SOD1 SOD1 G93A Gur transgenic males which resemble most clinical features of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The SOD1 G93A mice ( n = 48 were randomized divided into |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | four groups (1) 1 orally administrated vehicle 0.9% saline (SOD1 SOD1 group n = 12 (2) 2 orally administrated 4 mg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Among them 36 transgenic mice (SOD1 SOD1 group n = 9 FA-SOD1 group n = 9 B12-SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | 10 of the wild-type littermates at the same age as SOD1 G93A mice were used as controls for the histopathological staining |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The initial sign of disease in SOD1 G93A mice is resting tremor and progressive development of gait |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | SOD1 G93A mice (SOD1 SOD1 group n = 3 FA-SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | SOD1 G93A mice (SOD1 SOD1 group n = 3 FA-SOD1 mice n = 3 B12-SOD1 |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | used the primary antibody of glial fibrillary acidic protein (GFAP, GFAP 1 2000 Sigma St Louis MO USA and CD11b (1:100, |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | (GFAP, GFAP 1 2000 Sigma St Louis MO USA and CD11b (1:100, 1 100 Serotec Oxford UK to examine the activation |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | 0.45 _amp_#x3bc m PVDF membrane incubated with primary antibodies of iNOS (1:5000, 1 5000 Chemicon CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | primary antibodies of iNOS (1:5000, 1 5000 Chemicon CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 Cell signaling MA USA Bcl-2 (1:1000, 1 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 Cell signaling MA USA Bcl-2 (1:1000, 1 1000 Santa Cruz Biotechnology Inc. Santa Cruz cleaved |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | Cruz cleaved caspase-3 (1:1000, 1 1000 Cell signaling MA USA PARP and cleavage (1:1000, 1 1000 Cell signaling MA USA respectively |
| 132 | ACTB | actin, beta | beta-actin | 0.3 | Afterwards the blots were stripped and stained with beta-actin antibody (1:4000, 1 4000 Cell signaling MA USA |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | and B12 on the onset of symptoms and lifespan in SOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | or B12 treatment can influence the onset of symptoms in SOD1 G93A mice we analyzed the motor function of all animals |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | SOD1 G93A mice usually recapitulated the clinical progression of ALS by |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | of the onset of symptoms compared with the mice in SOD1 group (114.4 114.4 _amp_#xb1 1.7 116.3 _amp_#xb1 2.0 vs 107.9 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | In addition FA or FA B12 treated SOD1 G93A mice had significant 9-day and 13-day extension in lifespan |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | had significant 9-day and 13-day extension in lifespan compared with SOD1 group mice respectively (137.7 137.7 _amp_#xb1 1.9 141.4 _amp_#xb1 2.9 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | There was no significant difference between B12-SOD1 group and SOD1 group in the lifespan (132.3 132.3 _amp_#xb1 1.9 vs 128.8 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | was performed to examine the total plasma Hcy level in SOD1 G93A and wild-type litter mate mice at the age of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The level of Hcy in SOD1 group was 180% of the level in wild-type mice (6.84 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | 0.67 vs 6.84 _amp_#xb1 0.4 _amp_#x3bc;mol/L _amp_#x3bc mol L in SOD1 group mice ( Fig._amp_#xa0 2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | L vs 6.84 _amp_#xb1 0.4 _amp_#x3bc;mol/L _amp_#x3bc mol L in SOD1 group mice ( Fig._amp_#xa0 2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | alone could significantly reduce the level of Hcy in the SOD1 G93A transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | In SOD1 group mice at the age of 120 days there were |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | were 74.5% and 88.3% more motor neurons than mice in SOD1 group (383.5 383.5 _amp_#xb1 24.43 413.67 _amp_#xb1 32.48 vs 219.67 |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | In our study we used GFAP and CD11b to examine the status of microglia and astrocyte |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | In our study we used GFAP and CD11b to examine the status of microglia and astrocyte respectively in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | microglia and astrocyte respectively in the spinal cord sections of SOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | overwhelming microglial and astrocytic activation in the spinal cord of SOD1 G93A mice at the age of 120 days whereas the_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | activation between the mice treated with B12 alone and control SOD1 G93A mice ( Fig._amp_#xa0 4 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | significant increase in the_amp_#xa0 expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | in the_amp_#xa0 expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 al. 1999 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 al. 1999 Hensley et_amp_#xa0 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | Therefore in our study we examined the protein levels of iNOS and TNF-_amp_#x3b1 in the spinal cord of the mice |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | our study we examined the protein levels of iNOS and TNF-_amp_#x3b1 in the spinal cord of the mice |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | We_amp_#xa0 observed significant reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | We_amp_#xa0 observed significant reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice compared with |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice compared with mice in SOD1 group ( Fig._amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | group or FA SOD1 group mice compared with mice in SOD1 group ( Fig._amp_#xa0 5 A |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | FA B12 was more effective in lowing the level of iNOS ( Fig._amp_#xa0 5 C |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | results documented that the inflammation in FA-SOD1 group or FA SOD1 group was strongly suppressed compared with SOD1 group |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | group or FA SOD1 group was strongly suppressed compared with SOD1 group |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | drugs FA and B12 had the anti-apoptotic effects in the SOD1 G93A transgenic mice we determined the protein level of Bcl-2 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | SOD1 G93A transgenic mice we determined the protein level of Bcl-2 cleaved caspase-3 and PARP in the spinal cord after FA |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | we determined the protein level of Bcl-2 cleaved caspase-3 and PARP in the spinal cord after FA B12 or FA B12 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | FA or FA B12 treatment can increase the level of Bcl-2 and reduce the level of cleaved caspase-3 and cleaved PARP |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | Bcl-2 and reduce the level of cleaved caspase-3 and cleaved PARP ( Fig._amp_#xa0 5 B |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | we found FA B12 treatment can elevate the level of Bcl-2 in SOD1 G93A mice up to the level of wild-type |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | FA B12 treatment can elevate the level of Bcl-2 in SOD1 G93A mice up to the level of wild-type which could |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | that FA B12 is effective in suppressing apoptosis in the SOD1 mice model |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | B12 treatment significantly attenuates the increased level of Hcy in SOD1 G93A mice |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | treatment can suppress the production of inflammatory factors such as iNOS and TNF-_amp_#x3b1 and inhibit the activation of microglia and astrocytes |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | suppress the production of inflammatory factors such as iNOS and TNF-_amp_#x3b1 and inhibit the activation of microglia and astrocytes |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | or FA B12 treatment has significant anti-apoptotic effects by increasing Bcl-2 expression and inhibiting cleaved caspase-3 and cleaved PARP |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | by increasing Bcl-2 expression and inhibiting cleaved caspase-3 and cleaved PARP |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | that Hcy can enhance pro-inflammatory cytokines production such as interleukin-6 TNF-_amp_#x3b1 and C-reactive protein ( Holven et_amp_#xa0 al. 2006 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | (2007) 2007 reported that Hcy could increase the expression of TNF-_amp_#x3b1 which plays a critical role in inflammatory responses and apoptosis |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | Furthermore TNF-_amp_#x3b1 can switch resting murine astrocytes to active state and up-regulate |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | can switch resting murine astrocytes to active state and up-regulate iNOS expression and subsequently release nitric oxide ( Falsig et_amp_#xa0 al. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | In addition it was reported that the expression of iNOS was increased in the spinal cord of the SOD1 G93A |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | of iNOS was increased in the spinal cord of the SOD1 G93A transgenic mice and activated microglia and astrocytes increased the |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | mice and activated microglia and astrocytes increased the production of iNOS which suggest that iNOS may contribute to the pathology of |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | and astrocytes increased the production of iNOS which suggest that iNOS may contribute to the pathology of ALS and represent a |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | suppressed the glial activation as well as the expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | glial activation as well as the expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice at the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice at the age of 120 days |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Hcy may play a role in the increased inflammation of SOD1 G93A mice model and lowering the level of Hcy by |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | by regulating the expression of several important proteins such as Bcl-2 cleaved caspase-3 and cleaved PARP ( Baydas et_amp_#xa0 al. 2005 |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | several important proteins such as Bcl-2 cleaved caspase-3 and cleaved PARP ( Baydas et_amp_#xa0 al. 2005 and Kruman et_amp_#xa0 al. 2000 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | Bcl-2 plays a prominent role in ALS pathogenesis which is involved |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | Bcl-2 family is implicated in the regulation of motor neuron death |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | is implicated in the regulation of motor neuron death in SOD1 G93A transgenic mice model and over-expression of Bcl-2 can significantly |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | death in SOD1 G93A transgenic mice model and over-expression of Bcl-2 can significantly protect motor neurons in SOD1 G93A mice ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | and over-expression of Bcl-2 can significantly protect motor neurons in SOD1 G93A mice ( Kostic et_amp_#xa0 al. 1997 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | FA or FA B12 treatment can increase the expression of Bcl-2 which provided an evidence for the neuroprotective effect of FA |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | the neuroprotective effect of FA or FA B12 treatment in SOD1 G93A mice |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | Cleaved caspase-3 and cleaved PARP represent the downstream signals of apoptosis which may contribute to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | apoptosis which may contribute to the motor neuron death in SOD1 G93A mice ( Pasinelli et al. 2000 |
| 5215 | HSD17B7 | hydroxysteroid (17-beta) dehydrogenase 7 | PRAP | 1.0 | In addition reactive astrocytes could express cleaved PRAP in the central nervous system in SOD1 G93A mice ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | could express cleaved PRAP in the central nervous system in SOD1 G93A mice ( Chung et al. 2004 |
| 5215 | HSD17B7 | hydroxysteroid (17-beta) dehydrogenase 7 | PRAP | 1.0 | induce apoptosis in neuronal cells resulting from the activation of PRAP |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | FA B12 treatment could up-regulate the expression of anti-apoptotic protein Bcl-2 as well as down-regulated the expression of apoptosis-related proteins such |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | expression of apoptosis-related proteins such as cleaved caspase-3 and cleaved PARP |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | in the level of Hcy inflammation and apoptosis in the SOD1 G93A transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | a result inflammation and apoptosis remain high in B12 treated SOD1 G93A transgenic mice |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | FA B12 possessed anti-inflammatory effects through inhibiting the expression of iNOS and TNF-_amp_#x3b1 and suppressing the activation of microglia and astrocytes |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | possessed anti-inflammatory effects through inhibiting the expression of iNOS and TNF-_amp_#x3b1 and suppressing the activation of microglia and astrocytes |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | can significantly inhibit the levels of cleaved caspase-3 and cleaved PARP as well as up-regulate the levels of Bcl-2 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | and cleaved PARP as well as up-regulate the levels of Bcl-2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | and B12 on the disease onset and the lifespan of SOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | A and the probability of survival (B) B in the SOD1 group B12-SOD1 group FA-SOD1 group and FA B12-SOD1 group * |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Data showed that the level of Hcy in SOD1 group was increased as compared with the wild-type mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | FA B12-SOD1 group mice was significantly decreased as compared with SOD1 group mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | group # P _amp_#x3c 0.01 (when when compared with the SOD1 group * N in each group = 8 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | (a) a Wild-type group (b) b SOD1 group (c) c B12-SOD1 group (d) d FA-SOD1 group (e) |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | group # P _amp_#x3c 0.01 (when when compared with the SOD1 group * N in each group = 3 |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | CD11b and GFAP were used as the markers of microglia (red) |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | CD11b and GFAP were used as the markers of microglia (red) red and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | in FA-SOD1 or FA B12-SOD1 group mice as compared with SOD1 group mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | While there was no difference between B12-SOD1 group mice and SOD1 group mice * N in each group = 3 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | (A) A Western blot of iNOS and TNF-_amp_#x3b1 from spinal cord samples of G93A transgenic mice |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | (A) A Western blot of iNOS and TNF-_amp_#x3b1 from spinal cord samples of G93A transgenic mice in five |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | G93A transgenic mice in five groups (WT: WT wild-type group SOD1 SOD1 group B12 B12-SOD1 group FA FA-SOD1 group FA B12 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | transgenic mice in five groups (WT: WT wild-type group SOD1 SOD1 group B12 B12-SOD1 group FA FA-SOD1 group FA B12 FA |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | (B) B Western blot of Bcl-2 cleaved caspase-3 and cleaved PARP from spinal cord samples |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | (B) B Western blot of Bcl-2 cleaved caspase-3 and cleaved PARP from spinal cord samples |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | (C_amp_#x2013;G) C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | (C_amp_#x2013;G) C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 3.2 | C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | PARP | 1.9 | the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | and ## P _amp_#x3c 0.001 (when when compared with the SOD1 group * N in each group = 3 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | mutations in copper/zinc superoxide dismutase sod1 account for 20% cases of familial als fals but the underlying pathogenetic mechanisms are largely unknown. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | t fa or fa + b12 treatment significantly attenuated the plasma hcy level suppressed the activation of microglia and astrocytes and inhibited the expression of inducible nitric oxide synthase inos and tumor necrosis factor alpha tnf _amp_#x3b1; in spinal cord. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | furthermore we found that fa or fa + b12 treatment significantly attenuated the plasma hcy level suppressed the activation of microglia and astrocytes and inhibited the expression of inducible nitric oxide synthase inos and tumor necrosis factor alpha tnf _amp_#x3b1; in spinal cord. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | moreover fa or fa + b12 treatment decreased the levels of cleaved caspase 3 and poly adp ribose polymerase parp but up regulated the level of anti apoptotic protein bcl 2. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | moreover fa or fa + b12 treatment decreased the levels of cleaved caspase 3 and poly adp ribose polymerase parp but up regulated the level of anti apoptotic protein bcl 2. |
| 270 | PARP1 | poly (ADP-ribose) polymerase family, member 1 | poly adp ribose polymerase | 1.0 | moreover fa or fa + b12 treatment decreased the levels of cleaved caspase 3 and poly adp ribose polymerase parp but up regulated the level of anti apoptotic protein bcl 2. |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | we used the primary antibody of glial fibrillary acidic protein gfap 1:2000 sigma st louis mo usa and cd11b 1:100 serotec oxford uk to examine the activation of astrocyte and microglia respectively. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | each sample was separated in 8% sds gel transferred onto 0.45 _amp_#x3bc;m pvdf membrane incubated with primary antibodies of inos 1:5000 chemicon ca usa tnf _amp_#x3b1; 1:1000 cell signaling ma usa bcl 2 1:1000 santa cruz biotechnology inc. santa cruz cleaved caspase 3 1:1000 cell signaling ma usa parp and cleavage 1:1000 cell signaling ma usa respectively. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | _amp_#x3bc;m pvdf membrane incubated with primary antibodies of inos 1:5000 chemicon ca usa tnf _amp_#x3b1; 1:1000 cell signaling ma usa bcl 2 1:1000 santa cruz biotechnology inc. santa cruz cleaved caspase 3 1:1000 cell signaling ma usa parp and cleavage 1:1000 cell signaling ma usa respectively. |
| 132 | ACTB | actin, beta | beta actin | 1.0 | afterwards the blots were stripped and stained with beta actin antibody 1:4000 cell signaling ma usa . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | to investigate whether hcy lowering drugs fa and b12 had the anti apoptotic effects in the sod1 g93a transgenic mice we determined the protein level of bcl 2 cleaved caspase 3 and parp in the spinal cord after fa b12 or fa + b12 treatment. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | to investigate whether hcy lowering drugs fa and b12 had the anti apoptotic effects in the sod1 g93a transgenic mice we determined the protein level of bcl 2 cleaved caspase 3 and parp in the spinal cord after fa b12 or fa + b12 treatment. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | we found that fa or fa + b12 treatment can increase the level of bcl 2 and reduce the level of cleaved caspase 3 and cleaved parp fig._amp_#xa0;5 b . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | we found that fa or fa + b12 treatment can increase the level of bcl 2 and reduce the level of cleaved caspase 3 and cleaved parp fig._amp_#xa0;5 b . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | especially we found fa + b12 treatment can elevate the level of bcl 2 in sod1 g93a mice up to the level of wild type which could suggest that fa + b12 is effective in suppressing apoptosis in the sod1 mice model. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | moreover we demonstrated that fa or fa + b12 treatment has significant anti apoptotic effects by increasing bcl 2 expression and inhibiting cleaved caspase 3 and cleaved parp. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | moreover we demonstrated that fa or fa + b12 treatment has significant anti apoptotic effects by increasing bcl 2 expression and inhibiting cleaved caspase 3 and cleaved parp. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | interleukin 6 | 1.0 | it is suggested that hcy can enhance pro inflammatory cytokines production such as interleukin 6 tnf _amp_#x3b1; and c reactive protein holven et_amp_#xa0;al. 2006 . |
| 2367 | CRP | C-reactive protein, pentraxin-related | c reactive protein | 1.0 | it is suggested that hcy can enhance pro inflammatory cytokines production such as interleukin 6 tnf _amp_#x3b1; and c reactive protein holven et_amp_#xa0;al. 2006 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | hcy could induce apoptosis by regulating the expression of several important proteins such as bcl 2 cleaved caspase 3 and cleaved parp [baydas et_amp_#xa0;al. 2005] and [kruman et_amp_#xa0;al. 2000] . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | hcy could induce apoptosis by regulating the expression of several important proteins such as bcl 2 cleaved caspase 3 and cleaved parp [baydas et_amp_#xa0;al. 2005] and [kruman et_amp_#xa0;al. 2000] . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | bcl 2 plays a prominent role in als pathogenesis which is involved in the oxidative stress and in the mitochondria mediated apoptosis pasinelli et_amp_#xa0;al. 2004 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | bcl 2 family is implicated in the regulation of motor neuron death in sod1 g93a transgenic mice model and over expression of bcl 2 can significantly protect motor neurons in sod1 g93a mice kostic et_amp_#xa0;al. 1997 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | in our study we found that fa or fa + b12 treatment can increase the expression of bcl 2 which provided an evidence for the neuroprotective effect of fa or fa + b12 treatment in sod1 g93a mice. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | cleaved caspase 3 and cleaved parp represent the downstream signals of apoptosis which may contribute to the motor neuron death in sod1 g93a mice pasinelli et al. 2000 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | our study suggested that fa or fa + b12 treatment could up regulate the expression of anti apoptotic protein bcl 2 as well as down regulated the expression of apoptosis related proteins such as cleaved caspase 3 and cleaved parp. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | r study suggested that fa or fa + b12 treatment could up regulate the expression of anti apoptotic protein bcl 2 as well as down regulated the expression of apoptosis related proteins such as cleaved caspase 3 and cleaved parp. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | moreover we found that fa or fa + b12 treatment can significantly inhibit the levels of cleaved caspase 3 and cleaved parp as well as up regulate the levels of bcl 2. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | moreover we found that fa or fa + b12 treatment can significantly inhibit the levels of cleaved caspase 3 and cleaved parp as well as up regulate the levels of bcl 2. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | b western blot of bcl 2 cleaved caspase 3 and cleaved parp from spinal cord samples. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | b western blot of bcl 2 cleaved caspase 3 and cleaved parp from spinal cord samples. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | c_amp_#x2013;g quantitative data of the expression of inos tnf _amp_#x3b1; bcl 2 cleaved caspase 3 and cleaved parp in five groups. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | c_amp_#x2013;g quantitative data of the expression of inos tnf _amp_#x3b1; bcl 2 cleaved caspase 3 and cleaved parp in five groups. |