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A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration
N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) catalyzes the cleavage of membrane NAPEs into bioactive fatty-acid ethanolamides (FAEs). Along with this precursor role, NAPEs might also serve autonomous signaling functions. Here, we report that injections of 6-hydroxydopamine (6-OHDA) into...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828692/ https://www.ncbi.nlm.nih.gov/pubmed/31685899 http://dx.doi.org/10.1038/s41598-019-51799-1 |
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author | Palese, Francesca Pontis, Silvia Realini, Natalia Piomelli, Daniele |
author_facet | Palese, Francesca Pontis, Silvia Realini, Natalia Piomelli, Daniele |
author_sort | Palese, Francesca |
collection | PubMed |
description | N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) catalyzes the cleavage of membrane NAPEs into bioactive fatty-acid ethanolamides (FAEs). Along with this precursor role, NAPEs might also serve autonomous signaling functions. Here, we report that injections of 6-hydroxydopamine (6-OHDA) into the mouse striatum cause a local increase in NAPE and FAE levels, which precedes neuronal cell death. NAPE, but not FAE, accumulation is enhanced in mice lacking NAPE-PLD, which display a substantial reduction in 6-OHDA-induced neurotoxicity, as shown by increased survival of substantia nigra dopamine neurons, integrity of striatal dopaminergic fibers, and striatal dopamine metabolite content. Reduced damage is accompanied by attenuation of the motor response evoked by apomorphine. Furthermore, NAPE-PLD silencing protects cathecolamine-producing SH-SY5Y cells from 6-OHDA-induced reactive oxygen species formation, caspase-3 activation and death. Mechanistic studies in mice suggest the existence of multiple molecular contributors to the neuroprotective effects of NAPE-PLD deletion, including suppression of Rac1 activity and attenuated transcription of several genes (Cadps, Casp9, Egln1, Kcnj6, Spen, and Uchl1) implicated in dopamine neuron survival and/or Parkinson’s disease. The findings point to a previously unrecognized role for NAPE-PLD in the regulation of dopamine neuron function, which may be linked to the control of NAPE homeostasis in membranes. |
format | Online Article Text |
id | pubmed-6828692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68286922019-11-12 A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration Palese, Francesca Pontis, Silvia Realini, Natalia Piomelli, Daniele Sci Rep Article N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) catalyzes the cleavage of membrane NAPEs into bioactive fatty-acid ethanolamides (FAEs). Along with this precursor role, NAPEs might also serve autonomous signaling functions. Here, we report that injections of 6-hydroxydopamine (6-OHDA) into the mouse striatum cause a local increase in NAPE and FAE levels, which precedes neuronal cell death. NAPE, but not FAE, accumulation is enhanced in mice lacking NAPE-PLD, which display a substantial reduction in 6-OHDA-induced neurotoxicity, as shown by increased survival of substantia nigra dopamine neurons, integrity of striatal dopaminergic fibers, and striatal dopamine metabolite content. Reduced damage is accompanied by attenuation of the motor response evoked by apomorphine. Furthermore, NAPE-PLD silencing protects cathecolamine-producing SH-SY5Y cells from 6-OHDA-induced reactive oxygen species formation, caspase-3 activation and death. Mechanistic studies in mice suggest the existence of multiple molecular contributors to the neuroprotective effects of NAPE-PLD deletion, including suppression of Rac1 activity and attenuated transcription of several genes (Cadps, Casp9, Egln1, Kcnj6, Spen, and Uchl1) implicated in dopamine neuron survival and/or Parkinson’s disease. The findings point to a previously unrecognized role for NAPE-PLD in the regulation of dopamine neuron function, which may be linked to the control of NAPE homeostasis in membranes. Nature Publishing Group UK 2019-11-04 /pmc/articles/PMC6828692/ /pubmed/31685899 http://dx.doi.org/10.1038/s41598-019-51799-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Palese, Francesca Pontis, Silvia Realini, Natalia Piomelli, Daniele A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title | A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title_full | A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title_fullStr | A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title_full_unstemmed | A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title_short | A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration |
title_sort | protective role for n-acylphosphatidylethanolamine phospholipase d in 6-ohda-induced neurodegeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828692/ https://www.ncbi.nlm.nih.gov/pubmed/31685899 http://dx.doi.org/10.1038/s41598-019-51799-1 |
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