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Acetaldehyde and parkinsonism: role of CYP450 2E1
The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689266/ https://www.ncbi.nlm.nih.gov/pubmed/23801948 http://dx.doi.org/10.3389/fnbeh.2013.00071 |
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author | Vaglini, Francesca Viaggi, Cristina Piro, Valentina Pardini, Carla Gerace, Claudio Scarselli, Marco Corsini, Giovanni Umberto |
author_facet | Vaglini, Francesca Viaggi, Cristina Piro, Valentina Pardini, Carla Gerace, Claudio Scarselli, Marco Corsini, Giovanni Umberto |
author_sort | Vaglini, Francesca |
collection | PubMed |
description | The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and PD. |
format | Online Article Text |
id | pubmed-3689266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-36892662013-06-25 Acetaldehyde and parkinsonism: role of CYP450 2E1 Vaglini, Francesca Viaggi, Cristina Piro, Valentina Pardini, Carla Gerace, Claudio Scarselli, Marco Corsini, Giovanni Umberto Front Behav Neurosci Neuroscience The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and PD. Frontiers Media S.A. 2013-06-21 /pmc/articles/PMC3689266/ /pubmed/23801948 http://dx.doi.org/10.3389/fnbeh.2013.00071 Text en Copyright © 2013 Vaglini, Viaggi, Piro, Pardini, Gerace, Scarselli and Corsini. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Neuroscience Vaglini, Francesca Viaggi, Cristina Piro, Valentina Pardini, Carla Gerace, Claudio Scarselli, Marco Corsini, Giovanni Umberto Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title | Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title_full | Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title_fullStr | Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title_full_unstemmed | Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title_short | Acetaldehyde and parkinsonism: role of CYP450 2E1 |
title_sort | acetaldehyde and parkinsonism: role of cyp450 2e1 |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689266/ https://www.ncbi.nlm.nih.gov/pubmed/23801948 http://dx.doi.org/10.3389/fnbeh.2013.00071 |
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