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N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology

Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down’s syndrome have been associated with several mito...

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Detalles Bibliográficos
Autores principales: Arakawa, Motoki, Ito, Yoshihisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102236/
https://www.ncbi.nlm.nih.gov/pubmed/17853088
http://dx.doi.org/10.1080/14734220601142878
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author Arakawa, Motoki
Ito, Yoshihisa
author_facet Arakawa, Motoki
Ito, Yoshihisa
author_sort Arakawa, Motoki
collection PubMed
description Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down’s syndrome have been associated with several mitochondrial alterations Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical-scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies.
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spelling pubmed-71022362020-03-31 N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology Arakawa, Motoki Ito, Yoshihisa Cerebellum Original Article Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down’s syndrome have been associated with several mitochondrial alterations Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical-scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies. Springer US 2007-12-01 2007 /pmc/articles/PMC7102236/ /pubmed/17853088 http://dx.doi.org/10.1080/14734220601142878 Text en © Taylor & Francis 2007 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Arakawa, Motoki
Ito, Yoshihisa
N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title_full N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title_fullStr N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title_full_unstemmed N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title_short N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
title_sort n-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102236/
https://www.ncbi.nlm.nih.gov/pubmed/17853088
http://dx.doi.org/10.1080/14734220601142878
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