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Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction

Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrat...

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Autores principales: Jeon, Posung, Yang, Sungjun, Jeong, Hojoong, Kim, Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Association of Anatomists 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145842/
https://www.ncbi.nlm.nih.gov/pubmed/21829757
http://dx.doi.org/10.5115/acb.2011.44.2.135
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author Jeon, Posung
Yang, Sungjun
Jeong, Hojoong
Kim, Hyun
author_facet Jeon, Posung
Yang, Sungjun
Jeong, Hojoong
Kim, Hyun
author_sort Jeon, Posung
collection PubMed
description Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrated that induction of proteasomal dysfunction in animal models results in a phenotype similar to Parkinson's disease. Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2) in dopaminergic neuronal death induced by a proteasomal synthase inhibitor (PSI), additionally testing the hypothesis that WIN55.212.2 modulates cytoplasmic accumulation of parkin and α-synuclein, a key feature of proteasomal dysfunction in Parkinson's. WIN55.212.2 protects PC12 cells from PSI-induced cytotoxicity, concomitantly inhibiting PSI-induced polyADP ribose polymerase expression and activation of caspase-3. While PSI induces cytoplasmic accumulation of α-synuclein and parkin, WIN55.212.2 counters these effects. Interestingly, however, while PSI induces the activation and nuclear translocalization of nuclear factor κB, WIN55.212.2 potentiates this effect. These data are suggestive that WIN55.212.2 might confer a neuroprotective benefit in PSI-induced proteasomal dysfunction, and could further protect against neuronal degeneration stemming from cytoplasmic accumulation of α-synuclein and parkin. These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson's disease.
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spelling pubmed-31458422011-08-09 Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction Jeon, Posung Yang, Sungjun Jeong, Hojoong Kim, Hyun Anat Cell Biol Original Article Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrated that induction of proteasomal dysfunction in animal models results in a phenotype similar to Parkinson's disease. Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2) in dopaminergic neuronal death induced by a proteasomal synthase inhibitor (PSI), additionally testing the hypothesis that WIN55.212.2 modulates cytoplasmic accumulation of parkin and α-synuclein, a key feature of proteasomal dysfunction in Parkinson's. WIN55.212.2 protects PC12 cells from PSI-induced cytotoxicity, concomitantly inhibiting PSI-induced polyADP ribose polymerase expression and activation of caspase-3. While PSI induces cytoplasmic accumulation of α-synuclein and parkin, WIN55.212.2 counters these effects. Interestingly, however, while PSI induces the activation and nuclear translocalization of nuclear factor κB, WIN55.212.2 potentiates this effect. These data are suggestive that WIN55.212.2 might confer a neuroprotective benefit in PSI-induced proteasomal dysfunction, and could further protect against neuronal degeneration stemming from cytoplasmic accumulation of α-synuclein and parkin. These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson's disease. Korean Association of Anatomists 2011-06 2011-06-30 /pmc/articles/PMC3145842/ /pubmed/21829757 http://dx.doi.org/10.5115/acb.2011.44.2.135 Text en Copyright © 2011. Anatomy & Cell Biology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Jeon, Posung
Yang, Sungjun
Jeong, Hojoong
Kim, Hyun
Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title_full Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title_fullStr Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title_full_unstemmed Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title_short Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
title_sort cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145842/
https://www.ncbi.nlm.nih.gov/pubmed/21829757
http://dx.doi.org/10.5115/acb.2011.44.2.135
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