Randomized, Double-Blind, Controlled Trial of Acetylcysteine in Amyotrophic Lateral Sclerosis

Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling

“…Alternatively, the effect of N-acetylcysteine may depend on the type of ALS expressed. N-Acetylcysteine increased survival in a subgroups of patients with disease of the limbs onset, whereas it may have decreased survival in those with bulbar onset (Louwerse et al, 1995). This adds to existing data suggesting a different contribution of excitotoxicity in these types of ALS.…”

Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling

“…Alternatively, the effect of N-acetylcysteine may depend on the type of ALS expressed. N-Acetylcysteine increased survival in a subgroups of patients with disease of the limbs onset, whereas it may have decreased survival in those with bulbar onset (Louwerse et al, 1995). This adds to existing data suggesting a different contribution of excitotoxicity in these types of ALS.…”

Defects in Glutathione System in an Animal Model of Amyotrophic Lateral Sclerosis

“…Although accumulating evidence suggests a direct or indirect involvement of aberrant glutathione homeostasis and metabolism in ALS [40], it remains unclear whether reduced glutathione is a causative factor or a result of neurodegeneration in ALS. So far, clinical trials aiming to improve glutathione contents in ALS by supplementation have been ineffective [106,107], as well as clinical trials targeting Nrf2 activating substances [102][103][104][105]113]. In consideration of our results, the dysregulations observed cannot be reversed by Nrf2 activation alone.…”

The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils

“…beta-carotene, being the most extraordinary case, but the same holds true for vitamins C and E) have been observed in the majority of, if not all, clinical trials foreseeing antioxidant use in a great deal of human (including neurological) disorders [44,45]. For example, α-tocopherol, N-acetyl-L-cysteine or a combination of L-methionine, vitamin E and selenium, failed in terms of delaying amyotrophic lateral sclerosis progression in randomized, double-blind, placebo-controlled trials [46][47][48][49], a result confirmed by a meta-analysis of all antioxidants combined [50]. Similarly, antioxidant use appears to have a limited role in the prevention or treatment of Parkinson's disease and Alzheimer's disease [51][52][53][54].…”

Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling

“…Alternatively, the effect of N-acetylcysteine may depend on the type of ALS expressed. N-Acetylcysteine increased survival in a subgroups of patients with disease of the limbs onset, whereas it may have decreased survival in those with bulbar onset (Louwerse et al, 1995). This adds to existing data suggesting a different contribution of excitotoxicity in these types of ALS.…”

Defects in Glutathione System in an Animal Model of Amyotrophic Lateral Sclerosis

“…Although accumulating evidence suggests a direct or indirect involvement of aberrant glutathione homeostasis and metabolism in ALS [40], it remains unclear whether reduced glutathione is a causative factor or a result of neurodegeneration in ALS. So far, clinical trials aiming to improve glutathione contents in ALS by supplementation have been ineffective [106,107], as well as clinical trials targeting Nrf2 activating substances [102][103][104][105]113]. In consideration of our results, the dysregulations observed cannot be reversed by Nrf2 activation alone.…”

The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils

“…beta-carotene, being the most extraordinary case, but the same holds true for vitamins C and E) have been observed in the majority of, if not all, clinical trials foreseeing antioxidant use in a great deal of human (including neurological) disorders [44,45]. For example, α-tocopherol, N-acetyl-L-cysteine or a combination of L-methionine, vitamin E and selenium, failed in terms of delaying amyotrophic lateral sclerosis progression in randomized, double-blind, placebo-controlled trials [46][47][48][49], a result confirmed by a meta-analysis of all antioxidants combined [50]. Similarly, antioxidant use appears to have a limited role in the prevention or treatment of Parkinson's disease and Alzheimer's disease [51][52][53][54].…”

Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling

“…Alternatively, the effect of N-acetylcysteine may depend on the type of ALS expressed. N-Acetylcysteine increased survival in a subgroups of patients with disease of the limbs onset, whereas it may have decreased survival in those with bulbar onset (Louwerse et al, 1995). This adds to existing data suggesting a different contribution of excitotoxicity in these types of ALS.…”

Defects in Glutathione System in an Animal Model of Amyotrophic Lateral Sclerosis

“…Although accumulating evidence suggests a direct or indirect involvement of aberrant glutathione homeostasis and metabolism in ALS [40], it remains unclear whether reduced glutathione is a causative factor or a result of neurodegeneration in ALS. So far, clinical trials aiming to improve glutathione contents in ALS by supplementation have been ineffective [106,107], as well as clinical trials targeting Nrf2 activating substances [102][103][104][105]113]. In consideration of our results, the dysregulations observed cannot be reversed by Nrf2 activation alone.…”

The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils

“…beta-carotene, being the most extraordinary case, but the same holds true for vitamins C and E) have been observed in the majority of, if not all, clinical trials foreseeing antioxidant use in a great deal of human (including neurological) disorders [44,45]. For example, α-tocopherol, N-acetyl-L-cysteine or a combination of L-methionine, vitamin E and selenium, failed in terms of delaying amyotrophic lateral sclerosis progression in randomized, double-blind, placebo-controlled trials [46][47][48][49], a result confirmed by a meta-analysis of all antioxidants combined [50]. Similarly, antioxidant use appears to have a limited role in the prevention or treatment of Parkinson's disease and Alzheimer's disease [51][52][53][54].…”