)| PMID |
8922414 ( ) |
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| Title | Reduction of lower motor neuron degeneration in wobbler mice by N-acetyl-L-cysteine. |
| Abstract | The murine mutant wobbler is a model of lower motoneuron degeneration with associated skeletal muscle atrophy. This mutation most closely resembles Werdnig-Hofmann disease in humans and shares some of the clinical features of amyotrophic lateral sclerosis (ALS). It has been suggested that reactive oxygen species (ROS) may play a role in the pathogenesis of disorders such as ALS. To examine the relationship between ROS and neural degeneration, we have studied the effects of agents such as N-acetyl-L-cysteine (NAC), which reduce free radical damage. Litters of wobbler mice were given a 1% solution of the glutathione precursor NAC in their drinking water for a period of 9 weeks. Functional and neuroanatomical examination of these animals revealed that wobbler mice treated with NAC exhibited (1) a significant reduction in motor neuron loss and elevated glutathione peroxidase levels within the cervical spinal cord, (2) increased axon caliber in the medial facial nerve, (3) increased muscle mass and muscle fiber area in the triceps and flexor carpi ulnaris muscles, and (4) increased functional efficiency of the forelimbs, as compared with untreated wobbler littermates. These data suggest that reactive oxygen species may be involved in the degeneration of motor neurons in wobbler mice and demonstrate that oral administration of NAC effectively reduces the degree of motor degeneration in wobbler mice. This treatment thus may be applicable in the treatment of other lower motor neuropathies. Health, Mount Sinai Hospital, Toronto, Ontario, Canada. 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 |
|---|---|---|---|---|
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | 72 | NAC | NAC-treated | NAC-wobbler | |
| 1912 | CHAT | choline acetyltransferase | 4 | choline acetyltransferase | |
| 2169 | CNTF | ciliary neurotrophic factor | 1 | CNTF | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 1 | bcl 2 | |
| 1033 | BDNF | brain-derived neurotrophic factor | 1 | BDNF | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | the effects of agents such as N -acetyl-L -cysteine (NAC), NAC which reduce free radical damage |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | mice were given a 1% solution of the glutathione precursor NAC in their drinking water for a period of 9 weeks |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | examination of these animals revealed that wobbler mice treated with NAC exhibited (1) 1 a significant reduction in motor neuron loss |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | neurons in wobbler mice and demonstrate that oral administration of NAC effectively reduces the degree of motor degeneration in wobbler mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The compound N -acetyl-L -cysteine (NAC) NAC has been shown to inhibit ROS thus increasing the viability |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | In vivo NAC also has been shown to reduce the toxicity of compounds |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | In humans extensive clinical experience with NAC suggests that it is a compound of low toxicity most |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC seems to exert these effects by acting directly as an |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To examine the effects of NAC on motor neuron degeneration in vivo we treated wobbler mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | degeneration in vivo we treated wobbler mice per os with NAC over a period of 9 weeks |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The results demonstrate that NAC treatment reduces the decline in several important morphological and functional |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | solutions were adjusted to the same pH and molarity as NAC-treated animals (61.2 61.2 m M and served as control agents |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | Four-week-old NAC-treated mice drank an average of 3.4 _amp_#177 0.6 ml per |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The mean quantity of NAC ingested was ~2.3 mg/gm mg gm body weight |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The mean quantity of NAC received was 2.1 mg/gm mg gm body weight |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | Even within the NAC-treated group the distinction between wr/wr wr wr and NW mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | of the facial nerve for wr/wr wr wr NW and NAC-treated wr/wr wr wr and NW mice is shown in Figure |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | In NAC-treated wr/wr wr wr mice [wr/wr(N)] wr wr N this reduction |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | nerve as compared with NW controls wobbler animals treated with NAC do not show this loss of motor axons instead giving |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | the distribution of axon areas in wr/wr wr wr and NAC-treated wr/wr wr wr mice respectively |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | In contrast NAC-treated wobbler mice do not show a marked reduction in axon |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | the wobbler controls are significantly different from both the wr NAC treatment and NW groups pair-wise comparisons wr/wr wr wr vs |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | given above demonstrate that oral treatment of wobbler mice with NAC can reduce significantly the degree of axonal atrophy and loss |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To examine the effects of NAC on neuromuscular aspects of the forelimb we took 10 micro |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | neurons by 9 weeks of age wobbler mice treated with NAC exhibited significantly greater numbers of ChAT-positive neurons than wr/wr wr |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-wobbler | 0.3 | However NAC-wobbler mice still exhibited a substantial loss of ChAT-positive neurons as |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To determine the effects of NAC treatment on the innervation targets of these spinal motor neurons |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | As shown in Figure 4 A B animals treated with NAC show a significant increase in the overall mass of the |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Thus treatment with NAC reduces the degree of overt muscular atrophy that is induced |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To delineate more clearly the effects of NAC on muscle morphology within the distal forelimb we determined cross-sectional |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | shown in Figure 4 C indicate that animals treated with NAC show a marked increase in mean fiber area (~603 ~603 |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | These data demonstrate that oral administration of NAC can reduce significantly motor neuron loss and axonal atrophy in |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | These results demonstrate that although wobbler mice receiving NAC do exhibit a significant reduction in forelimb function they perform |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | These data suggest that treatment with NAC does result in some reduction in the functional losses that |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Previous work has suggested that NAC acts in part by increasing intracellular supplies of cysteine the |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To determine the ability of NAC to enhance the free-radical scavenging ability of the GPx system |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | As shown in Figure 6 animals that received NAC in their drinking water exhibited a substantial increase in GPx |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | similar to that of NW mice that did not receive NAC supplementation |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | To further assess the ability of NAC to effect GPx activity levels in non-wobbler mice we injected |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | (glucose glucose treatment group daily with 1 mg/gm mg gm NAC for 3 d before the analysis |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | These results demonstrate the ability of NAC to enhance antioxidant activity in tissues affected by the wobbler |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The results demonstrate that daily oral administration of NAC significantly reduces the degeneration of lower motor neurons in wobbler |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | For motor axons of the facial nerve application of NAC resulted in a generalized increase in axon number and caliber |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Within the cervical spinal cord NAC reduced losses of choline acetyltransferase-positive neurons |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC has been shown previously in several of these paradigms to |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | The ability of NAC to reduce the loss of these lower motor neurons in |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | in the cervical spinal cord suggests a means by which NAC may act to reduce local ROS levels |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Previous work also demonstrates that NAC directly supports glutathione synthesis in neural cells thus reducing intracellular |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | These data suggest that NAC may exert survival-promoting effects in a manner independent of its |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC has been used previously in a limited trial over a |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | no net clinical improvement was observed in patients treated with NAC segregation of ALS cases into bulbar and limb onset groups |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | In ALS cases of bulbar onset NAC did not improve survival |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | However in patients with the limb onset form NAC does seem to improve survival (NAC NAC 74% 28/38; 28 |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | limb onset form NAC does seem to improve survival (NAC NAC 74% 28/38; 28 38 vehicle 51% 22/43) 22 43 |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | It is interesting to speculate that the differential availability of NAC to these two neural populations may underlie the differences in |
| 2169 | CNTF | ciliary neurotrophic factor | CNTF | 0.3 | wobbler mice has been treated previously with a combination of CNTF (1 1 mg/kg) mg kg and BDNF (5 5 mg/kg) |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | a combination of CNTF (1 1 mg/kg) mg kg and BDNF (5 5 mg/kg) mg kg by subcutaneous injection three times |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | function over a similar time frame than those treated with NAC |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | For example to be accessible to motor neurons NAC must be taken up via contact with somatic tissue through |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Oral administration of NAC does result in enhanced GPx activity in the cervical spinal |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | axonal transport may be impaired in their ability to accumulate NAC and its metabolites thus limiting its potential therapeutic effects |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | In addition it is important to realize that NAC may be affecting only a portion of the pathways involved |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | Despite this the use of agents such as NAC would seem to be a practical approach to enhancing cell |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | intrathecal implantation of proteins which are quite labile in vivo NAC can be given per os over dispersed intervals |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC is also an inexpensive drug possessing few side effects and |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | to that of several human neurodegenerative disorders the application of NAC may prove useful in treating other mammalian neurodegenerative diseases |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC reduces axonal loss in wobbler facial nerve |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | Control-treated wr/wr wr wr mice n = 17 NAC-treated wr/wr wr wr mice n = 11 NW mice n |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC prevents losses in axon caliber in wobbler mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC-treated | 0.3 | C Axon distribution of NAC-treated wr/wr wr wr mice n = 6 |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC reduces the loss of ChAT-positive neurons in the cervical spinal |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC reduces the atrophy of forelimb muscles in wobbler mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC reduces functional losses in the forelimb of wobbler mice |
| 14374 | NLRP1 | NLR family, pyrin domain containing 1 | NAC | 0.3 | NAC treatment augments glutathione peroxidase (GPx) GPx levels in the cervical |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | the importance of ros in programmed cell death also has been suggested from the neuroprotective effects of bcl 2 family proteins which seem to act by inhibiting ros induced cell damage kane et al. 1993 ; zhong et al. 1993 ; myers et al. 1995 ; lawrence et al. 1996 . |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | histological analysis of the cervical spinal cord of wobbler mice demonstrates wallerian degeneration reductions in axon caliber and decreases in choline acetyltransferase chat activity within the anterior horn by 8 weeks of age bird et al. 1971 ; mitsumoto and bradley 1982 ; baulac et al. 1983 . |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | then every fifth section was stained for choline acetyltransferase. |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | within the cervical spinal cord nac reduced losses of choline acetyltransferase positive neurons. |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | total numbers of choline acetyltransferase positive neurons are indicated for each group n = 4 . |