N-Acetyl-cysteine (NAC)
Information on nutritional supplements people with ALS have been taking
Contents
Effects on ALS
Treatment with the antioxidant NAC caused a significantly prolonged survival and delayed onset of motor impairment in G93A mice compared to control mice. [2]
The systematic administration of NAC to R6/2 mice suppressed the activation of AMPK-α1, reduced neuronal toxicity, which was assessed by the activation of caspases, increased neuronal density, ameliorated ventricle enlargement, and improved motor dysfunction. This beneficial effect of NAC in vivo appears to be direct because NAC also reduced the activation of AMPK-α1 and the death of STHdh(Q109) cells upon elevated oxidative stress. [1]
Discussion threads on the ALSTDI forum
Regulated pathways
Suppresses AMPK-α1 activation.
References
[1] <bibtex> @article{Ju2014, abstract = {Huntington's disease (HD) is an autosomal dominant neurological disorder that is induced by a CAG trinucleotide expansion in exon 1 of the Huntingtin (HTT) gene. We previously reported that the abnormal activation of an important energy sensor, AMP-activated protein kinase $\alpha$1 (AMPK-$\alpha$1), occurs in the brains of mice and patients with HD, which suggests that this abnormal activation may contribute to neuronal degeneration in HD. In the present study, we demonstrated that the elevated oxidative stress that was evoked by a polyQ-expanded mutant HTT (mHTT) caused the abnormal activation of AMPK-$\alpha$1 and, subsequently, resulted in neurotoxicity in a striatal progenitor cell line (STHdh(Q109)) and in the striatum of a transgenic mouse model of HD (R6/2). The systematic administration of an antioxidant (N-acetyl-cysteine, NAC) to R6/2 mice suppressed the activation of AMPK-$\alpha$1, reduced neuronal toxicity, which was assessed by the activation of caspases, increased neuronal density, ameliorated ventricle enlargement, and improved motor dysfunction. This beneficial effect of NAC in vivo appears to be direct because NAC also reduced the activation of AMPK-$\alpha$1 and the death of STHdh(Q109) cells upon elevated oxidative stress. Moreover, the activation of AMPK enhanced the level of oxidative stress in STHdh(Q109) cells, in primary neurons of R6/2 mice, and in the striatum of two different HD mouse models (R6/2 and Hdh(150Q/+)), whereas the inhibition of AMPK reduced the level of oxidative stress. Collectively, our findings suggest that positive feedback regulation between the elevated oxidative stress and the activation of AMPK-$\alpha$1 contributes to the progression of HD.}, author = {Ju, Tz-Chuen and Chen, Hui-Mei and Chen, Yu-Chen and Chang, Ching-Pang and Chang, Chen and Chern, Yijuang}, doi = {10.1016/j.bbadis.2014.06.012}, issn = {0006-3002}, journal = {Biochimica et biophysica acta}, keywords = {AMP-Activated Protein Kinases,AMP-Activated Protein Kinases: metabolism,Animals,Apoptosis,Atrophy,Atrophy: metabolism,Atrophy: pathology,Blotting, Western,Cell Proliferation,Cells, Cultured,Corpus Striatum,Corpus Striatum: metabolism,Corpus Striatum: pathology,Disease Models, Animal,Humans,Huntington Disease,Huntington Disease: metabolism,Huntington Disease: pathology,Immunoenzyme Techniques,Mice,Mice, Transgenic,Nerve Degeneration,Nerve Tissue Proteins,Nerve Tissue Proteins: physiology,Neurons,Neurons: metabolism,Neurons: pathology,Oxidative Stress}, mendeley-groups = {nac}, month = sep, number = {9}, pages = {1668--80}, pmid = {24946181}, title = Template:AMPK-$\alpha$1 functions downstream of oxidative stress to mediate neuronal atrophy in Huntington's disease., url = {http://www.ncbi.nlm.nih.gov/pubmed/24946181}, volume = {1842}, year = {2014} } </bibtex>
[2] <bibtex> @article{Andreassen2000, abstract = {Increasing evidence implicates oxidative damage as a major mechanism in the pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the effect of preventative treatment with N-acetyl-L-cysteine (NAC), an agent that reduces free radical damage, in transgenic mice with a superoxide dismutase (SODI) mutation (G93A), used as an animal model of familial ALS. NAC was administered at 1\% concentration in the drinking water from 4-5 weeks of age. The treatment caused a significantly prolonged survival and delayed onset of motor impairment in G93A mice treated with NAC compared to control mice. These results provide further evidence for the involvement of free radical damage in the G93A mice, and support the possibility that NAC, an over-the-counter antioxidant, could be explored in clinical trials for ALS.}, author = {Andreassen, O A and Dedeoglu, A and Klivenyi, P and Beal, M F and Bush, A I}, issn = {0959-4965}, journal = {Neuroreport}, keywords = {Acetylcysteine,Acetylcysteine: pharmacology,Age Factors,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: drug therapy,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: physiopathology,Amyotrophic Lateral Sclerosis: prevention \& contro,Animals,Disease Models, Animal,Mice,Mice, Transgenic,Motor Activity,Motor Activity: drug effects,Motor Activity: physiology,Mutation,Mutation: physiology,Superoxide Dismutase,Superoxide Dismutase: genetics,Survival Rate}, mendeley-groups = {nac}, month = aug, number = {11}, pages = {2491--3}, pmid = {10943709}, title = Template:N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amyotrophic lateral sclerosis., url = {http://www.ncbi.nlm.nih.gov/pubmed/10943709}, volume = {11}, year = {2000} } </bibtex>
