Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases

Tardiolo, Giuseppe; Bramantı, Placido; Mazzon, Emanuela

doi:10.3390/molecules23123305

Cited by 209 publications

(174 citation statements)

References 143 publications

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“…It should further be mentioned that some of the drugs mentioned above have limits as pharmaceutical treatment of LAMA2-CMD, since deleterious effects upon long-term administration in humans have been noted (e.g., doxycycline and bortezomib). NAC, on the other hand, has been FDA-approved for children since 1963 and has a long-established safety record [66,67] and benefits in a wide range of diseases [68][69][70][71]. Vitamin E also has been also safely used in children with different diseases for years [72,73].…”

Section: Discussionmentioning

confidence: 99%

Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

et al. 2020

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Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy 2J /dy 2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy 2J /dy 2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

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Section: Discussionmentioning

confidence: 99%

Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

et al. 2020

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“…This enhancement was followed by an increment of glutathione concentrations in brain in all subjects. In another clinical trial, repeated oral NAC administrations were able to significantly increase different peripheral antioxidant parameters (catalase and glutathione redox ratio) with respect to baseline; however, brain glutathione levels resulted unchanged, probably due to the low oral NAC bioavailability. An overview of N ‐acetylcysteine effects in neurodegenerative diseases has been recently reported by Tardiolo et al…”

Section: Clinical Trialsmentioning

confidence: 94%

Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases

Martinelli

Pucci

Battaglini

et al. 2019

Adv Healthcare Materials

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Many central nervous system (CNS) diseases are still incurable and only symptomatic treatments are available. Oxidative stress is suggested to be a common hallmark, being able to cause and exacerbate the neuronal cell dysfunctions at the basis of these pathologies, such as mitochondrial impairments, accumulation of misfolded proteins, cell membrane damages, and apoptosis induction. Several antioxidant compounds are tested as potential countermeasures for CNS disorders, but their efficacy is often hindered by the loss of antioxidant properties due to enzymatic degradation, low bioavailability, poor water solubility, and insufficient blood–brain barrier crossing efficiency. To overcome the limitations of antioxidant molecules, exploitation of nanostructures, either for their delivery or with inherent antioxidant properties, is proposed. In this review, after a brief discussion concerning the role of the blood–brain barrier in the CNS and the involvement of oxidative stress in some neurodegenerative diseases, the most interesting research concerning the use of nano‐antioxidants is introduced and discussed, focusing on the synthesis procedures, functionalization strategies, in vitro and in vivo tests, and on recent clinical trials.

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“…shown here confirm the fact that OS increases VEGFA expression levels 20. This double result matches with the normalized miR-205-5p levels found after NAC exposure.NAC is a precursor of l-cysteine with scavenging properties and antioxidant effects, interacting with the antioxidant glutathione system 50,51. On the other hand, the addition of NAC normalized H 2 O 2 -induced ROS and VEGFA levels.…”

mentioning

confidence: 99%

Oxidative stress‐induced angiogenesis is mediated by miR‐205‐5p

Oltra

Vidal-Gil

Maisto³

et al. 2019

J Cellular Molecular Medi

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miR‐205‐5p is known to be involved in VEGF‐related angiogenesis and seems to regulate associated cell signalling pathways, such as cell migration, proliferation and apoptosis. Therefore, several studies have focused on the potential role of miR‐205‐5p as an anti‐angiogenic factor. Vascular proliferation is observed in diabetic retinopathy and the ‘wet’ form of age‐related macular degeneration. Today, the most common treatments against these eye‐related diseases are anti‐VEGF therapies. In addition, both AMD and DR are typically associated with oxidative stress; hence, the use of antioxidant agents is accepted as a co‐adjuvant therapy for these patients. According to previous data, ARPE‐19 cells release pro‐angiogenic factors when exposed to oxidative insult, leading to angiogenesis. Matching these data, results reported here, indicate that miR‐205‐5p is modulated by oxidative stress and regulates VEGFA‐angiogenesis. Hence, miR‐205‐5p is proposed as a candidate against eye‐related proliferative diseases.

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Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases

Cited by 209 publications

References 143 publications

Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases

Oxidative stress‐induced angiogenesis is mediated by miR‐205‐5p

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